Bio-Physic in BME, Part-3 ..Topic - Biophysics of Neural Spike

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BIO-PHYSIC IN BIO-MEDICAL
ENGINEERING UNDERGRADUATE
PROGRAM [PART-3]

CHAPTER-13 : BIO-PHYSICS-OF-THE-NEURAL-SPIKE, My blog -->
www.scribd.com/guidebio-medicaleng1, TEXT-BOOK NAME:
INTRODUCTORY-BIO-PHYSICS BY FREDERICK-ROSS-
HALLELT,P.A.SPEIGHT,ROBERT-HENRY-STINSON-WG

8/14/2014

MOHAMMAD-SIKANDER-KHAN-LODHI

BIO-PHYSIC IN BIO-MEDICAL ENGINEERING UNDERGRADUATE PROGRAM [PART-3]
CHAPTER-13 : BIO-PHYSICS-OF-THE-NEURAL-SPIKE, My blog --> www.scribd.com/guidebio-medicaleng1, TEXT-BOOK NAME:
INTRODUCTORY-BIO-PHYSICS BY FREDERICK-ROSS-HALLELT,P.A.SPEIGHT,ROBERT-HENRY-STINSON-WG

BIO-MEDICAL ENGINEERING GUIDE BY SIKANDER-KHAN-LODHI | BIO-PHYSIC OF NEURAL
SPIKE
2-OF-42

Table of Contents
CHAPTER-13 : BIO-PHYSICS-OF-THE-NEURAL-SPIKE ..................................................................................... 2
13-1 INTRODUCTION: ................................................................................................................................... 2
13-2 ELECTRICAL-POTENTIALS-AT-BIOLOGICAL-CELL-MEMBRANES: .......................................................... 3
CONDUCTIVITY IN-BIOLOGICAL[NEURON]-CELL-MEMBRANE: ............................................................... 4
Table 13-3 ............................................................................................................................................... 12
13-3 PROPAGATION-OF-THE-NEURAL-SPIKE:- .......................................................................................... 18
HOW-BIO-SIGNAL GO DOWN A STREAM TO THE AXON: ................................................................... 24
LENGTH-CONSTANT: ........................................................................................................................... 25
PATCH-CLAMP-RECORDINGS: .................................................................................................................... 26
NERVE-IMPULSES-ARE-PROPAGATED-IN-ALL-or-NONE-FASHION: ......................................................... 28
HOW-CAN-WE-STUDY-ION-CHANNELS? ..................................................................................................... 31
List of Figures : ....................................................................................................................................... 32

CHAPTER-13 : BIO-PHYSICS-OF-THE-NEURAL-SPIKE
Bio-physics of Neural-spike are used to study in Neural-Network Application in bio-medical engineering !
13-1 INTRODUCTION:
i. We often correlate the relative positions of organisms on the evolutionary ladder with their
relative abilities to receive and process information from their environment.
ii. These abilities are directly related to the relative complexity of their sensory and nervous
systems .
iii. Basic to these nervous systems is their function, the controlled flow of information from one
part of the organism to another.
iv. The information is in the form of electrical-signals, called neural-spikes , which arise from
precisely determined movements of ions through membranes of specially designed cells.
v. While the field of electronics is primarily concerned with the flow of electrons, not ions,
there are certain aspects of the subject which are of great value in helping us to understand
the mechanisms involved in the production and propagation of the neural-spike.

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13-2 ELECTRICAL-POTENTIALS-AT-BIOLOGICAL-CELL-MEMBRANES:
i. Neurons, the cells which carry the neural-spike, are highly specialized for the purpose [see
fig 13-1].
ii. Most incoming signals (often chemical in nature) are received at the dendrites which are
fairly long fiber-like projections from the cell-body .
iii. Then signals are converted into the neural spike in a part of the cell body known as the
axon-hillock.
iv. The spike then propagates[propagates = goes] itself down the axon( which is another
projection of the cell-body usually much longer than the dendrites . its length is often
measured in meters, a distance which is comparable to the lengths of arms or legs of even
the largest species).
v. As in the case with all biological cells, the neuron is surrounded by a membrane about 5nm
thick, even throughout the length of the axon .
vi. Schwann-cell: Most of the axons in the more advanced organisms, such as mammals, are
further enwrapped by several double layers of membrane from another cell called a
Schwann-cell.
vii. Nodes-Of-Ranvier: => These additional layers of membrane, termed Myelin , do not
extend continuously down the axon. Instead they are segmented by small gaps, which
known as the Nodes-Of-Ranvier.
viii. In axons with no myelin, such as those found in squid or lobster, the neural-spike
propagates like a burning fuse by mechanisms which will be described in a following
section.
ix. In myelinated axons , the neural-spike appears only at the nodes of Ranvier. In either case,
its the axon-membrane which plays the major-role.
x. One function of the membrane is simply to retard the passage of selected ions and
molecules.
xi. BIOLOGICAL-CURRENT: Ions , however, are electrically charged particles and the flow of
such particles is really an electrical current.
xii. Any current, I, whether the flow of ions through a membrane or electrons in a wire is
measured in amperes [A].
xiii. An ampere[A] of current[I], flowing for one second, amounts to one coulomb of electrical
charge passing a given point.
xiv. Each positive or negative charge such as that carried by sodium-ions (Na
+
) or chloride-ions
(Cl
-
) is [-> q = 1.6x10
-19
] coulombs.
xv. CURRENT-DENSITY [I
d
] : The concept of Current density[ I
d
], is very useful , especially in
membranes where it is directly related to the rate of flow of ions through a unit area ;

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[
];
CONDUCTIVITY IN-BIOLOGICAL[NEURON]-CELL-MEMBRANE:
xvi. The ability of ions to pass through a membrane depends on the size , length, shape , and
chemical properties of any pores which are present on the membrane.
xvii. All these characteristics are lumped together into a single parameter, [sigma = = The
conductivity of the pore on the membrane of neuron ].
xviii. the membrane conductivity (g
m
) is given by equation 13-2:
[
]; [unit for g
m
=>
or
];
Where -> [ =the conductivity of pore on membrane ] ;
xix. where n in eq-13-2 is the number of pores per unit area=>
[ ];.
xx. Conductivity has units of siemen which are equal to inverse ohms (
). Typically units for

g
m
are =>
or
. In order to find the actual conductance (g) of a

particular area (A) of membrane one must use the relationship which is shown in
equation 13-3 .
[
];
[ -> g = actual-conductance, current =>
];
[
coulombs ];
xxi. The values of the membrane conductivity differ for each ion species because each ion has a
characteristic size and charge.
xxii. Ions also differ in the amount of water they bind. Table 13-1 lists some of the common ions
and their corresponding g
m
values for squid axon membrane.
xxiii. In any real system such as the squid axon , the internal and external ion concentrations are
fairly constant and hence total combined ion membrane conductivity can also be quoted.
Table 13-1
Membrane Conductivity Values
for Squid Axon Membrane
(Resting)
Ion g
m


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Combined ion 140x10
-5

K
+
37x10
-5

Na
+
1.1x10
-5

Cl
-
30x10
-5

xxiv. The motion of ions both inside and outside membranes is partly due to electrical-forces
arising from electrical charges nearby .
Example:
The squid-axon has a radius of 0.25x10
-3
cm , and a membrane conductivity of 1.4x10
-3

.
Find the conductance of one centimeter of squid-Axon. The area of the axon is circunlference times
length
Data:
Given:
r = 0.25x10
-3
cm.
g
m
= 1.4x10
-3

.
l = 1 cm = length of axon ;
REQUIRED:
g = ?
SOLUTION:
[
];
From equation 13-3,
[
];
[
];

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[
]; Answer ;
-----------finished--------
xxv. The force (F) on a particular ion , having charge q
1
is given by equation 13-4.
[
];
xxvi. Where E is the electric-field at this ion[q
1
] due to other charges in the vicinity. If there is
only one charge (q
2
) producing the field (E
2
) at the ion[ q
1
], then , see equation 13-5;
[
];
xxvii. Which , when combined with eq- (13-4) , leads to coulombs law: see equation 13-6.
[Coulombs-law => :
];
xxviii. In these equations [eq-> 13-6] (
) is the distance between the electrical-charge (q

2
) and
the ion, k is a constant having a value 9.0x10
+9
N.m
2
.C
-2
and K is the di-electric constant,
a property of the material between the charges q
1
and q
2
. Note that if K is very large then
the field experienced by the ions is relatively quite small.
xxix. Table 13-2 contains some dielectric constants for some common biological and non-
biological substances.
xxx. Note the very high value for water , a property which in aqueous solution makes the
electric-fields due to electrical charges fall off very rapidly with distance from the charge.
*Membrane-Components.
Table 13-2
Dielectric constants of selected
materials near 20C.
Air 1.007
Transformer
Oil
2.10
*Palmitic-Acid 2.30
Linoleic acid 2.60

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*Stearic-Acid 2.30
Beeswax 2.80
Wood 5.0
Membrane
(Approximate)
6.0
Casein 6.5
Ethanol 24.3
Water 80.4
xxxi. Equation 13-6 described the force on an ion[q
1
] due to a single charge[q
2
] nearby . this
charge[q
2
] could be a charge on a bio-polymer or on another ion.
xxxii. The microscopic environment of biological membranes contains large numbers of ions and
charged polymers . thus the net force on any one ion is due to the combination of the
electric fields of all these charges.
xxxiii. However, each field is a vector quantity (see chapter 7) and has a direction (due to the sign
and direction of the charge) and a magnitude (due to the proximity and size of the charge).
Thus the field experienced by any one ion is the vector sum of all the individual fields.
xxxiv. To illustrate this suppose we had a distribution of ions as shown in fig 13-2(a) and desired to
find the field at the position X. [ E=electric-field ], see figure 13.2 ;
xxxv. Where [k=9.0x10
+9
Nm
2
.C
-2
=constant = di-electric constant, a property of the material
between the charges q
1
and q
2
] , [ r
1-2
= The distance between the electric-charge(q
2
) and
the ion(q
1
) ].
xxxvi. The magnitudes and directions of the field at X due to each charge are shown and then
added vectorially in figure 13-2 (b) to produce the resultant-field of magnitude E.
WORK (W) :
a. Work(W) must be done to move any charged particle into an electric-field.
b. Hence , any charged species in an electric-field has a potential-energy equal to the work done
getting it there .
c. Consider , for example the work done in bringing a single charge (such as on an ion of charge q
1
)
into the electric-field of a fixed charge q
2
.
d. The little demon in figure 13-3 would have to do work equal to force times distance or [ see
equation 13-7]. And see figure 13.3 .

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[
];
e. Note that in equation 13-7 , an integration must be performed because the electric-field due to
the fixed charge gets larger as one gets closer to it.
f. Inserting equation 13-5 for E and integrating yields , see equation 13-8 below .
[
];
[
];
[
];
{:. [
]; }
{:.
}
[
];
g. This equation is often written =>

]; Volts.
Electric potential[V] :
h. Where V, the electric-potential[V] , is [see equation 13-10];
[Electric-Potential [V] =>
];
Example :
Find the resultant force on the sodium ion (Na
+
) in the environment of calcium ions (Ca
2+
) and
chloride ions (Cl
-
) shown below . all ions lie in the same plane and the solvent is water .see Fig-A,
The magnitudes of the individual fields are (using equation (13-5)):
[
];
[
];

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[
];
These fields can then be added vectorially using geometric methods or by components. See fig B
From the length of the resultant vector [E] the field at the sodium ion is about [ E=3.5x10
6
NC
-1
] .
thus the force on the sodium ion is given by equation (13-4).
[
];
[
];
Finished here this example:
i. Electric potential[V] has units of joules per coulomb or volts . its therefore , often called
voltage.
j. Note that its a property of the electric-field and is independent of the charge[ q
1
].
k. The electric-potential or voltage at a particular-point in a network of charged particles is not a
vector quantity as was the electric-field .
l. It is the sum of all the voltages
due to the particles placed at distance [
] , from the point of

interest. Thus , see equation 13-11 ,
[ absolute-voltages=>

];
m. Usually absolute-voltages as described above are not useful because experimentally only
voltage-differences can be measured.
--------
Example:
i. In neural-cells, for example, the voltage-difference across the membrane is typically in the
neighbourhood of -60 millivolts . that is , the inside of the membrane has an electrical
potential which is 60 millivolts lower than the exterior.
ii. Many membranes are permeable to small ions such as chloride (Cl
-
) and sodium(Na
+
), but
are impermeable to charged molecules.
iii. In this case, a stable voltage-difference across the membrane can be produced simply by a
re-arrangement of ion concentrations on either side .
iv. In order to see how this comes about imagine the circumstances shown in figure 13-4.
v. Originally the two compartments contained solutions of sodium chloride.
vi. A soluble sodium salt, NaQ, was then added to the inside compartment and this salt ionized
to produce sodium ion and a large singly charged species [Q
-
].

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42

vii. A semi-permeable membrane separates the two compartments. It allows free passage of
Na
+
and Cl
-
, but its pores are too small to let the negatively charged large species (Q
-
)
through .
viii. For chloride ion, sodium ion, and the charged species the concentration of electronic charge
in moles per litre is the same as their concentration in moles per litre because each carries
one electrical charge.
ix. Inside, the concentration of charge is [Cl
-
]
I
moles per litre for Cl
-
and [Na
+
]
I
moles per liter for
Na
+
and outside [Cl
-
]
o
and [Na
+
]
o
respectively.
x. By using the very simple ideas that like charges repel and unlike charges attract it can be
seen that the tendency of the negatively charged species would be to push chloride ions
outside and pull sodium ions inside. Of course as soon as this happens a voltage-difference
develops between the two sides.
xi. An equilibrium will be achieved when all forces balance. This equilibrium, called a Donnan-
equilibrium is characteristic to circumstances such as shown in figure-13-4, and can easily
be demonstrated in the laboratory.
xii. Its also possible to quantitatively calculate the equilibrium voltage difference, V
eq
, as well as
the equilibrium ion concentrations [Cl
-
]
o
, [Cl
-
]
o
, [Na
+
]
I
and [Na
+
]
o
.
xiii. First it must be realized that the whole system in figure 13-4 is at thermal equilibrium.
xiv. When such a situation holds the Boltzmann equation (ch-10) may be applied to indicate
how the ions should be distributed between the two potential energies (inside and outside).
xv. Considering chloride ions first and using equation 13-9 , for the ion potential-energies the
Boltzmann equation becomes.
[Boltzmann-equation=> :
];
[
];
xvi. In this equation N and N correspond to the numbers of chloride ions inside and outside
respectively.
xvii. If these are changed to the molar concentrations [Cl
-
]
I
and [Cl
-
]
o
then we must also replace
the Boltzmann constant k by the gass constant, R (R=8.32 J mol
-1
K
-1
) and q by its
corresponding molar quantity, n where , the faraday, is the total charge in coulombs of
one mole of singly charged ions, and n is the number of charges carried by the ion. has a
value of 96,500 coulombs per mole.thus
[
];

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xviii. Which can also be written as
[Nernst-equation:=>
];
xix. This equation is known as the Nernst-equation. Note that it precisely relates the
equilibrium voltage drop across the membrane [ called the membrane potential ] to the ion
concentrations on either side.
If these same relationships are applied to the sodium ion then one obtains, see eq-13-15
[
];
And
[
];
Note also by comparing equation 13-13 and equation 13-15 that ,
[
];
An equation which is extremely valuable in finding the equilibrium values of the ion concentrations.
There are two other equations which relate the concentrations of ions at equilibrium for a case such
as that of figure 13-4.
First of all , the total ion concentration is constant so that
[
];
And
[
];
Secondly , each side of the system is very nearly neutral. The slight differences is concentration required
to establish the membrane potential are negligible . that is , the amount of positive charge must equal
the amount of negative charge on each side . therefore see eq-13-20 and 13-21.
[
];
And
[
];

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42

Table 13-3 outlines the important equations which allow one to find the ion concentrations at Donnan-
equilibrium.
----
:.
[ ]; [=Faraday = Total charge in coulombs of one mole of singly charged ions=96,500
coulombs/mole.];
[=Number of charges carried by ion];
[
];
[
];
-------------finished-this-example-here----
Table 13-3
Equations for finding Ion concentrations at Donnan-Equilibrium
1 Thermal
Equilibrium
[
];
2

Conservation
of ions
i. [
];
ii. [
];

3

Neutrality i. [
];
ii. [
];

Next-Example:
Question:
i. Two compartments of a solution are separated by a semi-permeable membrane which
allows free passage of ions but blocks any transfer of macro-molecules .

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ii. A solution of sodium hyaluronate (which ionizes as shown in below fig-C , to produce a
negatively charged polyelectrolyte and sodium ions ) is placed in the inside compartment
and a salt solution is added to both sides .
iii. The initial concentrations are shown below . Assume a temperature of 20C.
iv. What will be the ion concentrations in the compartments and the membrane-potential
when Donnan-equilibrium is reached?
See Fig-C below :
Solution :
The equations from table 13-3 which correspond to this case are following:
i. From Thermal Equilibrium:=> [
];
ii. From Neutrality :=> [
];
iii. From Neutrality :=> [
];
iv. From Conservation of ions :=> [

];
v. From Conservation of ions:=> [

];
To solve these equations we need to eliminate all but one variable say , for example , [Na
+
]
o
, begin
with equation (v).
[
];
Using equation i and iii this can be converted to
{:.from Thermal-Equilibrium of table 13-3 [
];
{:. [
]; }
[
];
By placing the above equation in eq-v , we get !
[
];
Using eq-iii again
[
];

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42

[
];
Using eq-iv
[
];
{:. [
]; }
[
];
Or
[
];
Therefore ,
[
];
[
];
Using eq-iii
[
];
Using eq-v
[
];

[
];
[
];
Using eq-iv
[
];
[
];
[
];

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42

The final concentrations are given below chart
In-side cell membrane Outside cell
membrane
ion concentrations ion Concentration
Q
-
0.075 mol/l ---- ---
Na
+
0.149 mol/l Na
+
0.106 mol/l
Cl
-
0.074 mol/l Cl
-
0.106 mol/l
Answer-1
The cell-membrane potential can be found using either the chloride ions or sodium ions . thus from
equation 13-14:
[Nernst-equation:=>
];
Where :
[
];
So,
[
]; [
];
From equation 13-16
[
];
[
];
[
];
-------------Finished-here-this example----------
WORK [ countinue ]:

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42

n. The property of the membrane which allows a Donnan-type equilibrium to established is that it
contain pores which are large enough to allow the passage of ions, but too small to allow poly-
electrolytes passes through the cell membrane .
o. There is no requirement that the membrane be of biological origin and many synthetic
membranes work just fine . sometimes , when the poly-electrolyte concentration is very high its
necessary to make corrections to membrane potentials due to osmotic effects.
p. Over the years the development and improvement of micro-electrodes and sensitive electronic
equipment has made the measurement of membrane potentials a reasonably straight-forward
procedure. It is possible to measure membrane potentials in live axons and watch how these
potentials change as the neural spike passes.
q. Normally, if the neural-cell is alive, but not stimulated (that is, producing neural-spikes) the axon
membrane has a resting potential of about -60mV . other types of cells , such as muscle cells,
also have a characteristic resting potential .
r. Using equations 13-14, and eq-13-16 its possible to estimate what the concentration ratios
(inside/outside) would be for ions such as Na
+
, Cl
-
and K
+
if the axon membrane behaved like the
one in the previous example.
s. Table 13-4 shows the results of such calculations and the concentration ratios found
experimentally for squid axon.
Table 13-4
Concentration ratios (calculated Assuming Donnan-Equilibrium and
Experimentally measured in squid Axon)
Ion Ratio Calculated-Value
using Equations
(13-14) and (13-
16)
Experimental-Ratios
[Cl
-
]
i
/[Cl
-
]
o
9.1x10
-2
10x10
-2

[K
+
]
i
/[K
+
]
o
11 20
[Na
+
]
i
/[Na
+
]
o
11 0.11
t. The concentration ratios calculated and measured for chloride ion are very close, indicating that
this species is , indeed, very near equilibrium. For potassium and especially sodium there is no
agreement at all between the calculated and measured ratios.
u. There is somewhat more potassium inside than expected and about one hundred times less
sodium inside than expected .

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42

v. The system is in a much higher energy state than would be expected if thermal processes alone
were involved .
w. Thus , as far as these two ions are concerned , the membrane system is very far from Donnan-
equilibrium.
x. Using equation 13-16, one would expect that the measured values of the sodium and potassium
concentration ratios should yield membrane potentials of about +55mV and -75mV respectively.
y. Using equation 13-14, the corresponding potential for chloride ion is -58mV. These values ,
along with the resting potential, are shown in fig 13-5.
z. In order to maintain the sodium ion and potassium ion concentration ratios described earlier,
its necessary for these ions to be actively pumped through the membrane. In the case of sodium
ions, not only do they have to be transferred from inside to outside, but this has to be done
against an electric-potential difference and against a huge sodium ion concentration gradient.
This process requires a sizeable amount of energy so that the membrane has to have all the
machinery for converting chemical energy (usually from the molecule adenosine triphosphate)
into a form usable by the sodium pumps.
aa. Thus the resulting membrane is in a state of dynamic equilibrium , dependent on the energy
supply available. The only time a biological membrane such as this reaches Donnan-
equilibrium is after death.
bb. The dynamic-equilibrium associated with an axon membrane at resting potential is designed to
maintain the ion concentration ratios at the values listed in table 13-4 . for this to happen the
net ionic current density, I
d
, through the membrane must be zero.
cc. Ohms Law states that current is related to potential-difference and conductance by the
equation 13-22 below.
[ ];
dd. If membrane conductivity is used then this equation becomes, see eq-(13-23). Below.
[
];
ee. Where I
d
is the current density described earlier. For the resting membrane,see equation 13-24
[
];
ff. Since the terms due to other ions are fairly small it is possible to calculate the resting membrane
potential,
, using the membrane conductivity values from table 13-1 and the ionic potentials
from figure 13-5.
gg. The resulting value (about -65 mV) compares favorably with the experimental values of about -
60mV mentioned earlier especially in view of the relative un-certainties present in the values
for the membrane conductivities and the ionic potentials.

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42

hh. It is clear that the axon membrane is a finely tuned system. The conductances are precisely
determined for each ion to give the appropriate resting potential values.
ii. The pumps are set to maintain the ion concentration ratios (inside/outside) at precisely the right
level by pumping excess ion which leaks through right back again.
jj. It is felt in some quarters that the operation of the sodium pump controls potassium and
chloride ion ratios by default although this has not been clearly established at this time .
kk. The detailed operation of the ion pumps is not well understood at all. {:.
= resting membrane
potential }
13-3 PROPAGATION-OF-THE-NEURAL-SPIKE:-

i. When an electric-potential of about 20mV is applied to a small section of axon membrane
at resting-potential a momentary cataclysmic event take place.
ii. Its almost as if the membrane temporarily forgets its a membrane and becomes a sieve
instead.
iii. The sodium and potassium ions, which had previously been held at the concentration ratios
give in table13-4 suddenly strive to achieve Donnan-equilibrium values.
iv. The result is the neural-spike which is shown in figure 13-6 as a plot of membrane potential
against time in milli-seconds.
v. The spike is a relatively strong (about +40mV) , but short-lived (about 1 milli-second)
positive potential which moves rapidly down the axon.
vi. Just prior to the spike there is a shoulder, the pre-spike potential, which is the response due
to the applied 20 mV potential.
vii. Notice that the pre-spike potential increases to a potential about fifteen millivolts above the
resting potential. At this point, the threshold potential, the membrane conductance
properties suddenly changes and the positive spike develops.
viii. The exact structural or functional mechanism behind this change is not known but is the
subject of a great deal of research.
ix. During the pre-spike potential and the spike itself the axon membrane is said to be
depolarized because the potential is above the resting level.
x. Just following the spike the membrane becomes hyper-polarized (more negative than
resting potential) for a few milliseconds. During the first part of this period, the so-called
absolute refractory period, a second spike cannot be initiated at all.
xi. Later in the hyper-polarized period it is possible but more difficult to initiate a second spike
because a greater pre-spike potential has to be supplied to raise the potential to the
threshold-level .

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xii. The hyper-polarization period is , therefore, a kind of busy signal or dead time.
xiii. A better understanding of the neural-spike can be obtained if the sodium and potassium
conductivities are followed during the event.
xiv. These quantities are shown in figure 13-7. The change in sodium conductivity is incredible ,
from a value of 0.01x10
-3

prior to threshold to a peak value of about 30x10

-
3
, a factor of about a thousand .

xv. The change in potassium conductivity is not so spectacular (0.3x10
-3

to about
10x10
-3

) but sizeable nevertheless.

xvi. The huge increase in sodium conductivity causes a massive current of sodium ions (at least
at the microscopic level) and this current of positive charge causes the inside of the axone to
become positively charged with respect to the outside.
xvii. Effectively the sodium ions are striving to reach their equilibrium potential of +55mV. They
never quite make it it , however, become (a) their local concentration is depleted and (b) the
sodium conductivity rapidly returns to its resting value.
xviii. The spike is positice for only a very brief period because potassium ions are flowing out in an
attempt to reach their own equilibrium potential of -75 milli-volts.
xix. This outgoing positive current balances the earlier incoming current and the membrane
quickly returns to the resting potential.
xx. Additional out-flux of potassium continues for several milliseconds and leads to the
hyperpolarized refractory period.
xxi. In about 3 milli-seconds the membrane has returned to resting potential and is ready to fire
again .
xxii. Because of the dead-time associated with the refractory period the maximum firing rate is
about 300 spikes per second.
xxiii. The neural-spike which has just been described travels down as axon by a mechanism which
has some similarities to an electrical-pulse travelling down a cable.
xxiv. In contrast to the cable situation through the neural-spike never loses its positive amplitude
of +55mV, regardless of the length of the axon .
xxv. An ordinary electrical-pulse in a cable would gradually lose its amplitudethe longer the
cable, the greater the reduction in amplitude.
xxvi. However , a combination of cable theories with the special properties of the axon
membrane does provide a reasonable mechanism for spike propagation.
xxvii. First it must be recognized that at any instant the neural-spike has depolarized only a very
small fraction of the total axon length.
xxviii. The depolarized region is shown schematically and highly magnified in figure 13-8.
xxix. Inside the spike-region the membrane potential is positive , reaching a maximum value of
about 40mV. This potential can be represented by the symbol
.

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xxx. Outside the spike region the spike potential gradually decreases as would be expected in
any electrical cable.
xxxi. The value of the spike potential at some distance away from the spike region can be
represented by V* .
xxxii. The electric-field associated with the spike potential exerts a force which tends to move the
ions located nearby.
xxxiii. Longitudinal internal and external ion currents as well as membrane currents result as
shown in figure 13-9. See fig 13.9 .and also see fig 13.8 .
xxxiv. The current-densities I
d
which are of specific importance are the Internal longitudinal
current-density, (
) , down the axon and small leakage-current density(
) through the
membrane outside the spike region (
).
xxxv. In order to evaluate the importance of these currents in the propagation of the spike it is
necessary to consider in greater detail the concepts related to conductivity and resistivity in
the axon.
xxxvi. Since resistivity is just the inverse of conductivity any comments regarding one will also
apply to the other.
xxxvii. There are two resistivities associated with the axon which determine the current densities I
m

and I
l
. they are respectively the membrane resistivity and the longitudinal core resistivity
and the longitudinal core resistivity of the interior of the axon.
xxxviii. The membrane resistivity is just the inverse of the membrane conductivity which has
already been discussed. Therefore
[
];
R
m
= the Membrane-resistivity;
g
m
= membrane conductivity;

= the resistivity[
] which is associated with the interior of the axon ( the axoplasm) is a

somewhat different quantity from
because it is a volume property rather than a surface

property.
xxxix. Below threshold the values of R
m
for various ionic species are the inverse of the
corresponding g
m
values in Table 13-1.
xl. The resistance of any particular area (A) of the membrane may be obtained from the
relationship .
[
];
xli. The resistivity (
) associated with the interior of the axon (the Axo-plasm) is a somewhat

different quantity from
because it is a volume property rather than a surface property.


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xlii. The resistance of a specified volume of axoplasm is given by eq-13-27,
[
];
Where in this case A is the cross-section area of the volume and L is the length of the volume.
------------Finished-here------
[
= Internal-longitudinal-current-density(
) down the axon.];

[
= small-leakage-current-density(
) through the membrane outside spike region ];

[Spike-Potential= V* ];
Example:
The resistivity of the squid axon axoplasm is about 30cm. Find the resistance[R] of an axon 10cm
long, having a radius of 0.025 cm. from equation 13-27 ?
Solution:
[
];
{:.
= the resistivity[
] which is associated with the interior of the axon ( the axoplasm) is a somewhat
different quantity from
because it is a volume property rather than a surface property. }

Given :

cm;
L=10cm ;
Radius= r = 0.025 cm;
Required :
R=?
A=?
Solution:
For A:
A= .r
2
= .( 0.025 )
2
=

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[
];
[
Ohm ];
-----Finished------
Its sometimes convenient to express axon resistance on a per unit length basis such as
per centimeter of length. Since the axon is cylindrically shaped then from equation 13-
26. The membrane resistance for 1 cm of Axon is given by eq-13-28.

[
];
And from equation 13-27, longitudinal resistance per unit length see equation 13-29,
[
];
Where r is the radius of the axon . its these quantities which are related to the membrane and
longitudinal current densities.
From Ohms law , the magnitude of
depends on the voltage-difference [or gradient],

dV*/dx (the rate of change of V* with distance(x) from the spike region) along the axon
and the actual resistance per unit length of the axoplasm (
). Thus see eq-(13-

30).
[ ];
[
];
[
];
The negative sign in equation 13-30, arises because current is conventionally considered
to flow from more positive to less positive potentials. If the membrane was a perfect
insulator and no leakage current of ions occurred then
would be a constant.
Below threshold, membranes do have some small conductivity values , however , and
decrease with distance from the spike because of this leakage .

The value of the membrane current density is equal to the rate at which the longitudinal
current density decreases along the axon: see eq-13-31:
[
];

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{:. x = distance between the region where V* measured and the location from where spike originated =
distance from spike. }
In other words the longitudinal current which is lost appears as membrane current. In addition,
from Ohms law its also true that
at a point on the membrane is given by , see eq-(13-32).

[
];
Where
V* = the potential difference at that point due to the spike potential, and
= the membrane resistance of a unit length.

Note that this equation applies only to regions of the membrane where the potential is below threshold.
From equations 13-31, and eq-13-32 and the differentiation of equation 13-30
[
];
[
];
[
];
[
];
[
];
[
];
The solution to this differential equation is
[
];
However V* must approach zero at distance , x, which are very large and hence the stant , B,
must be zero.
When x is zero, V* must equal the spike potential which means that A is equal to
. thus

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[

];
[x>>0]; [(V*0) at x ];
And V* is seen to fall of exponentially with distance from the spike-region. Notice that V*
decreases to 1/e of its original value when x has a magnitude of (r.R
m
/2.R
l
)
1/2
.this distance is
a characteristic of all electrical cables and is called the length constant.
The exponential character of V* is shown in figure 13-10 for squid axons of two different radii.
[
];
See fig 13.10
--
Example:
For the squid axon the membrane resistivity R
m
=700
and the longitudinal core resistivity
=30. Typically the squid axon has a radius of 0.25mm or 0.025 cm. Find (a) the length-constant
associated with the axon and (b) the distance from the spike-region at which the potential due to the
spike reaches +15mV. Assume [
].?
Solution:
For a:
The Length constant:
[
];
For b:
Using equation 13-33 and result from above part-a.
[
];
HOW-BIO-SIGNAL GO DOWN A STREAM TO THE AXON:
The example above demonstrates that the positive potential due to the spike extends a sizeable
distance down the axon from the spike region into a region which is still at resting potential.

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This positive potential acts exactly as the earlier applied potential and produces a pre-spike
potential in the new region. If the value of V* is greater than the potential required to exceed
the threshold potential then a new spike is produced and a new spike region develops
downstream from the first one.
The same ion movements occur and a new spike of the same amplitude as the first one is
generated. This new spike will in turn lead to the production of a new one still further
downstream and the process continues down the full length of the axon .
Spike propagation thus takes place with no loss of amplitude in the transmission process.
The mechanism of spike propagation is therefore closely involved with the dynamic-equilibrium
which characterizes the resting membrane, and with the physics contained in equation 13-35.
--
LENGTH-CONSTANT:
The length-constant, which comes from this equation can also be used to estimate the
propagation velocity of the spike as it moves down the axon.
Figure 13-10 also demonstrates the length-constants of two axons differing only in their radii.
The axon with the larger radius has a larger length-constant and the magnitude of the potential
V* falls off more gradually with distance down the axon .
In this axon, the first spike can initiate a new one in a more distant region of the fiber than is
possible in the smaller diameter axon. Therefore , in larger axons the spike propagates with
bigger steps and travels faster .
The velocity of spike propagation is thus proportional to the length constant: see equation 13-
36.
[
]; its the velocity of the spike-propagation.

For axons having the same values of R
m
and
equation 13-36 can be re-arranged to yield :

[
];
Or
[
];
Equation 13-38, is useful for comparing the propagation velocity of spikes in similar axons with different
radii.

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Its of significant benefit to larger animals to have fast reaction times. This can be achieved by
the system evolving axons which have large radii, such axons would take up more space,
however, and space is at a premium.
The significance of this becomes apparent it , for example , one considers the opticnerve bundle
of the eye, which contains about
axon fibres. If each one had a radius of 0.05 cm, the radius
of the squid-axon , then the total cross-sectional area of the optic-nerve bundle of the eye
would have to be about 8000 cm
2
. This is many times larger than the cross-section of the eye
itself.
More advanced species such as mammals have reduced the axon radius and increased R
m

extensively. This is the role of myelination which we described at the beginning of the chapter .
The neural spikes in these systems appear only at the gaps in the myelin, the so-called nodes-of-
Ranvier.
The spike at one node produces a potential which causes the pre-spike potential at the next.
Thus in these systems the spike hops from node to node and the transmission speed is ,
therefore, much faster.
As a result, the myelinated nervous cells of these animals can carry a great deal more
information and with extremely high efficiency.
This beneficial effect of increasing R
m
is also apparent from equation 13-36.
There are many other fascinating topics in the biophysics of neural-systems which cannot be
covered here.
Its a rapidly growing field , spurred on by the possibility that eventually we may be able to
understand how the brain a highly complex neural-system, functions.
For the interesting student we suggest such book as nerve,muscle and synapse by Bernar katz and
membranes, ions and Impulses by KC.Cole for further reading .
--------------Finished-here-------
PATCH-CLAMP-RECORDINGS:
i. In the patch clamp technique, a small patch of membrane is sealed by suction to the end of
a micro-pipette, enabling investigators to record currents through single membrane
channels , see figure .
ii. Erwin Neher and Bert sakmann were awarded the Noble prize in 1991 for devising this
technique.
iii. Patch clamp recordings have been made not only in nerve cells but also in glial-cells and
muscle cells.
iv. The recordings show that the channels open abruptly and remain open only briefly .

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v. Opening of some channels is made more likely by change in voltage; these are the voltage-
gated channels we described earlier. As we have seen , one example is the voltage-activated
sodium channel that is responsible for the rising phase of the nerve impulse.
vi. This type of channel responds extremely rapidly. Channels of the other main family respond
to chemical substances applied to the surfaces of the cell; their responses are slower than
those of the voltage-gated channels..
vii. Examples of these chemically gated channels will come up a little later in this chapter when
we discuss what happens at synapses.

Figure 3.6 Patch clamp recording from a single ion channel.
---------Finished-here, Patch clamp-recording----------

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NERVE-IMPULSES-ARE-PROPAGATED-IN-ALL-or-NONE-FASHION:
i. Now that we have explored the characteristics of a nerve-impulse at a single location on the
axon, we can ask how the axon communicates nerve impulses along its entire length .
ii. To examine this process, we place recording electrodes at several points along the axon (fig
3.7) . the nerve impulse is initiated at one end of the axon, and recordings are made with
electrodes placed along the length of the axon.
iii. These recordings show that the nerve impulse appears with increasing delays at the
successive positions along the length of the axon.
iv. The nerve-impulse initiated at one location on the axon spreads in a sort of chain reaction
along the length, traveling at speeds that range from less than 1 m/s in some fibers to more
than 100m/s in others.
v. How does the nerve impulse travel? The nerve impulse is a change in membrane potential
that is regenerated at successive axon locations. It spreads from one region to another
because the flow of current associated with this small and rapid change in potential
depolarizes and thus stimulates adjacent axon segments.
vi. That is (as we noted earlier) , the nerve impulse regenerates itself at successive points
along the axon. An analogy is the spread of fire along a row of closely spaced matches.
When one match is lit, the heat associated with its flame can be hot enough to start fire in
an adjacent match and so on along the row . Voltage-gated sodium channels open when the
axon is depolarized to threshold. In turn, the influx of sodium ionsthe movement into the
cell of positive chargesdepolarizes the adjacent segment of axon membrane and therefore
opens new gates for the movement of sodium ions.
vii. The axon normally conducts impulses in only one direction because the action potential
starts at the axon hillock.[Axon hillock = its the place where the axon emerges from the cell
body].
viii. As the action potential progresses along the axon, it leaves in its wake a stretch of refractory
membrane .
ix. Propagated activity does not spread from the hillock back over the cell body and dendrites,
because the membrane of the cell body and of most dendrites does not produce a
regenerated impulse.
x. If we record the conduction speed of impulses in axons that differ in diameter, we see that
the rate of conduction varies with the diameter of the axon.
xi. In mammals, relatively large, heavily myelinated fibers are found in sensory and motor
nerves . in these neurons conduction speed ranges from about 5 m/s in axons that are 2m
in diameter to 120 m/s in axons that are 20m in diameter.
xii. Although once thought to be as great as the speed of light, the highest speed of neural
conduction is only about one-third the speed of sound in air.

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xiii. This relatively high rate of conduction aids the speed of sensory and motor processes (fig
3.8) .
xiv. The myelin sheathing on the larger mammalian nerve fibers greatly speeds conduction. The
myelin is interrupted by the nodes of Ranvier , [nodes of Ranvier = small gaps spaced about
every millimeter along the axon (See fig 2.6). ] . since the myelin insulation offers
considerable resistance to the flow of ionic currents., the impulse jumps from node to
node. This process is called salutatory-conduction (from the latin saltus, a leap or jump)
(fig 3.8b).
xv. The evolution of rapid salutatory conduction in vertebrates has given them a major
behavioral advantage over invertebrates, in which axons are unmyelinated and mostly small
in diameter, and thus slow in conduction.
xvi. One exception to this rule is that many invertebrates have a few giant axons, which mediate
behaviorally significant motor responses, such as escape movements .
xvii. In the invertebrate as in the vertebrate, the speed of conduction increases with axon
diameter.

Figure 3.7 Propagation of a Nerve Impulse along the Axon: the farther the recording electrode is from
the site of stimulation, the later the action potential reaches it . however, the size of the action potential
is same at each point along the axon.

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-

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----------------finished------
HOW-CAN-WE-STUDY-ION-CHANNELS?

i. Lets look briefly at present concepts of the structure of ion channels and then consider how
investigators have been able to determine these structures.
ii. The membrane is a double layer of lipids whose fatty nature tends to repel water. Because
ions in water or body fluids are usually surrounded by clusters of water molecules, they
cannot easily pass through neuron membranes.
iii. Instead, they penetrate the cell through special channels, the inner surfaces of which do not
repel water (see fig 3.4) .
iv. The ion channels in neuron membranes are too tiny to be seen in detail even with the
electron microscope .
v. How then can investigators determine their structures and modes of operation? Three main
techniques have been used , providing more complete knowledge about ion channels.
vi. Molecular genetic analysis of potassium and sodium channels in a variety of cells including
muscles and neurons has yielded a detailed portrait of ion channel structure and function.
Some of these studies have come from the scrutiny of abnormalities in sodium and
potassium channel function that underlie particular human diseases.
vii. For example, some heritable muscle disorders characterized by loss of muscle tone or
paralysis involve abnormalities in the sodium channels of muscle that include an impairment
of the inactivation gate for sodium (S.C. Cannon, 1996).
viii. These studies reveal that multiple genes encode the structure and function of ion channel
proteins. Other researchers use pharmacology or patch clamp techniques, which we
describe next.
PHARMACOLOGICAL-TECHNIQUES:
i. Pharmacological experiments use certain toxins of animal origin to block specific ion
channelssome affecting the activation gate near the outer end of the channel, and others
inhibiting the inactivation gate at the inner end of the channel.
ii. By specifically blocking only some channels these toxins make it easier to study the
remaining channels.
--------------CHAPTER-13 ON BIO-PHYSICS , FINISHED-HERE---------

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List of Figures :


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13.8

+ 13.9

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----------Bio physics of-Neural-Spike Finished-here-------------
---------Finished-------


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Bio-Physic in BME, Part-3 ..Topic - Biophysics of Neural Spike

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qwertyuiopasdfghjklzxcvbnmqwertyui

). Typically units for

. In order to find the actual conductance (g) of a

) is the distance between the electrical-charge (q

due to the particles placed at distance [

] , from the point of

prior to threshold to a peak value of about 30x10

, a factor of about a thousand .

) but sizeable nevertheless.

) , down the axon and small leakage-current density(

] which is associated with the interior of the axon ( the axoplasm) is a

because it is a volume property rather than a surface

) associated with the interior of the axon (the Axo-plasm) is a somewhat

because it is a volume property rather than a surface property.

) down the axon.];

) through the membrane outside spike region ];

because it is a volume property rather than a surface property. }

depends on the voltage-difference [or gradient],

). Thus see eq-(13-

decrease with distance from the spike because of this leakage .

at a point on the membrane is given by , see eq-(13-32).

= the membrane resistance of a unit length.

and the longitudinal core resistivity

]; its the velocity of the spike-propagation.

equation 13-36 can be re-arranged to yield :

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