‫אנטומיה ופיזיולוגיה של האדם א'‬

‫קורס ‪65211‬‬

‫‪:‬חלק א‬
‫מבוא לפיזיולוגיה של תא העצב ומערכת העצבים‬
‫ד"ר אהרון טרואן‬
‫‪troen@agri.huji.ac.il‬‬
‫בנין גד"ש ישן (קנדי לי) חדר ‪112‬‬
‫שעות קבלה‪ :‬בתאום מראש‪ ,‬יום ג' ‪10-12‬‬
 Nutrition and Neuroscience
Nobel Prize in Physiology or Medicine 1929

Christiaan Eijkman
For his discovery of “Anti Neuritic Vitamin”
Sir Frederick Gowland Hopkins
For his discovery of the “growth-stimulating vitamins"

"Christiaan Eijkman - Nobel Lecture". Nobelprize.org. 13 Feb 2011

http://nobelprize.org/nobel_prizes/medicine/laureates/1929/eijkman-lecture.html
 Nobel Prizes in Nutrition Science
Nobel Prize in Physiology or Medicine Nobel Prize in Chemistry
Discovery of Vitamins   Synthesis of Vitamins  
Christiaan Eijkman (1929) Vitamin B1 Walter Norman Haworth (1937) Vitamin C
Sir Frederick Gowland Hopkins (1929) Growth Stimulating Vitamins Paul Karrer (1937) Vitamin E
George Hoyt Whipple (1934)* Vitamin B12 Robert Burns Woodward (1965)* Vitamin B12
George Richards Minot (1934)* Vitamin B12  
Structure of Vitamins
William Parry Murphy (1934)* Vitamin B12
Paul Karrer (1937) Vitamin A and B
Henrik Carl Peter Dam (1943) Vitamin K
Richard Kuhn (1938) Vitamin B2
Isolation of Vitamins  
Lord (Alexander R.) Todd (1957)* Vitamin B12
Adolf Otto Reinhold Windaus (1928)* Vitamin D
Dorothy Crowfoot Hodgkin (1964)* Vitamin B12
Albert von Szent-Györgyi Nagyrapolt Vitamin C
(1937)
Richard Kuhn (1938) Vitamin B2 and B6
Edward Adelbert Doisy (1943) Vitamin K

The Nobel Peace Prize (1949) - Lord (John) Boyd Orr of Brechin
(Scientist, MD; Director of Rowett Institute, Scotland; Director General of UN FAO)

 "The Nobel Prize and the Discovery of Vitamins". Nobelprize.org. 13 Feb 2011
http://nobelprize.org/nobel_prizes/medicine/articles/carpenter/index.html
 The Human Brain

• ~100 Million Neurons, ~ 1000 million cells

• 2% Body Weight
• 15% Cardiac Output
• 20-30% Resting Metabolic Rate
• No Storage Tissue
Nerve Cells
 Outline
• Membrane Potential
• Resting Potential
• The Nerve Cell
• Action Potentials
• Glial Cells
• Central Nervous System
• Autonomic Nervous System
– Sympathetic
– Parasympathetic
Cell Membranes and Transporters

- - -
+ - +
- + + +

- + - -
- + -
+ + +
 The cell membrane
• Diffusion
• Osmosis
• Passive Transprt
• Active Transport
• The ionic basis of membrane potential
 Excitable Membranes
• Resting potential
• Presynaptic potential – depolarization and
hyperpolarization
• Ion Channels
• Propagating action potentials
 Transport across cell membranes
• Simple diffusion
• Facilitated Diffusion
• Primary Active Transport
• Co-transport
• Counter-transport
• (Endocytosis)

X
+ X+

in out
Simple Diffusion
 Simple Diffusion
Permeable membrane

J (mmol/sec) = P (cm/sec) A (cm2) (CA- CB) (mmol/L)

J = net rate of diffusion; P = permeability; A = surface area for diffusion; C = concentration
 Facilitated Diffusion
Semi permeable – selective membrane
t0
 Facilitated Diffusion
Semi permeable – selective membrane
t∞
 Diffusion
Transport Rate

Carrier mediated transport - Tm

si on
diffu
p le
Sim

Concentration
 Osmosis
Semi permeable membrane
t0
 Osmosis
Semi permeable membrane
t∞
 Osmosis
Semi permeable membrane




p (atm) = g (Osm/mol) C (mmol/L) s (0-1) RT

p = osmotic pressure ; g = N particles /mol solution; C = concentration; s = reflection coefficient
R = gas constant (0.82 L-atm/mol-K); T = absolute temperature K
 Tonicity / Osmolarity
[NaCl ] = 1 mol/L [Urea] = 2 mol/L

+
+
- -
-
+

p (atm) = g (Osm/mol) C (mmol/L) s (0-1) RT

p = osmotic pressure ; g = N particles /mol solution; C = concentration; s = reflection coefficient
R = gas constant (0.82 L-atm/mol-K); T = absolute temperature K
 Tonicity / Osmolarity
[NaCl ] = 1 mol/L [Urea] = 2 mol/L

+
+
- -
-
+
Osmolarity = g (number particles / mol) C (concentration mol/L)
NaCl: 2 x 1 mol/L = 2 Osm/L
Urea: 1 x 2 mol/L = 2 Osm/L
Solutions are isosmotic

p (atm) = g (Osm/mol) C (mmol/L) s (0-1) RT

p = osmotic pressure ; g = N particles /mol solution; C = concentration; s = reflection coefficient
R = gas constant (0.82 L-atm/mol-K); T = absolute temperature K
 Tonicity / Osmolarity
[NaCl ] = 1 mol/L [Urea] = 2 mol/L

+
+
- -
-
+
Tonicity = p (atm) = g (Osm/mol) C (mmol/L) s (0-1) RT
RT 37⁰C=25.45 L •atm/mol
sNaCl: 0.3  p NaCl = 2 x 1mol/L x 0.3 = RT = 0.6RT = 15.3 atm
sUrea: 0.05  p Urea = 1 x 2mol/L x 0.05 = RT = 0.1RT = 2.5 atm
! Solutions are not isotonic

p
 Tonicity / Osmolarity
[NaCl ] = 1 mol/L Hypertonic [Urea] = 2 mol/L Hypotonic

+
+
- -
-
+
Tonicity = p (atm) = g (Osm/mol) C (mmol/L) s (0-1) RT
RT 37⁰C=25.45 L •atm/mol
sNaCl: 0.3  p NaCl = 2 x 1mol/L x 0.3 = RT = 0.6RT = 15.3 atm
sUrea: 0.05  p Urea = 1 x 2mol/L x 0.05 = RT = 0.1RT = 2.5 atm
! Solutions are not isotonic

p H20
Electrogenic Transport
Semi permeable – selective membrane

- -
- + - +
+ +
- -
+ +
 Membrane Potential
Selective membrane – permeable to K+, impermeable to Cl-
0
t0
-V+

+ + +
- - + -
+ -
- +
+ +
- - -

[K+Cl-] in > [K Cl ] + -
out

Concentration gradient
 Membrane Potential
Selective membrane – permeable to K+, impermeable to Cl-
0
t∞
-V+

+ + - +
- - -
+ +
+ - - -
+ +
-

[K+][Cl-] in > [K+][Cl-] out

Concentration gradient Potential (voltage) gradient

=
 Active Transport: Na+/K+ ATPase
Na+
K+

Na+ Na+
Na+ K+

Na+
Na+ K+ Na+
Na+

Na+

Na+

Na+

K+ Na+ K+
Na+ Na+
K+

K+ K+ K+ K+
Na+
 Na+/K+ ATPase
Na+
K+

Na+ Na+
Na+ K+

Na+
Na+ K+ Na+
Na+

Na+
Na+
Na+
Na+
Na+
ATP Na+
K+ K+
Na+
K+

K+ K+ K+ K+
 Na+/K+ ATPase
Na+
K+

Na+ Na+
Na+ K+

Na+
Na+ K+ Na+
Na+

Na+

Na+ Na+

Na+

P
K+ K+
Na+
K+ ADP

K+ K+ K+ K+
 Na+/K+ ATPase
Na+
K+ Na+
Na+
Na+
Na+ Na+
K+

Na+
K+
Na +
Na+
Na+

Na+

Na+ Na+

Na+

P
K +
K+
Na+
K+
ADP

K+ K+ K+ K+
 Na+/K+ ATPase
Na+ Na+ Na+
K+
Na+
Na+
Na+ K+

Na+
K+
Na +
Na+
Na+

K+ Na+

K+

P
K+ K+
Na+
K+

K+ K+ K+ K+
 Na+/K+ ATPase
Na+ Na+ Na+
K+
Na+
Na+
Na+

Na+
Na+ Na+
Na+

K+ Na+

K+

P
K+ K+
Na+
K+

K+ K+ K+ K+
 Na+/K+ ATPase
Na+ Na+ Na+
K+
Na+
Na+
Na+

Na+
Na+ Na+
Na+

K+

K+

K+ K+
Na+
K+ Pi

K+ K+ K+
K +
 Na+/K+ ATPase
Na+ Na+ Na+
K+
Na+
Na+
Na+

Na+
Na+ Na+
Na+

K+

K+

K+

K+ K+
Na+
K+ Pi

K+ K+
K+ K + K+
K +
 Na+/K+ ATPase
Na+ Na+ Na+
K+
Na+
Na+
Na+

Na+
Na+ Na+
Na+

K+

K+

K+

K+ K+
Na+
K+ Pi

K+ K+
K+ K + K+
K +
 Na+/K+ ATPase
3Na+in 3Na+out

E-P E-P
ADP + Pi
ATP
E E-P
2K +
in
2K+out
 Transport across cell membranes
+ + + + + + + K+
Simple diffusion
Na+ Cl -
--------
CO2 Na+ K+
Cl -

02
Na+

Glucose Facilitated Diffusion

Glucose
Co-transport (Symport)
 Electrochemical Equillibrium
[ X  ]in
  X )  in  X )   out  X )  RT ln 
  
zF ( Ein  Eout )
[ X ]out

X + X+

in out

Concentration gradient Potential (voltage) gradient

=
 Equilibrium Potential
Nernst Equation: Ex = -2.3 RT/zF (log10 [X]in /[X]out )
E = equilibrium potential (mV)
2.3RT/F = constant (~60 mV at 37⁰C)
Z = charge on the ion (+1 for Na+ & K+; -1 for Cl-; +2 for Ca+2 etc.)

Membrane Potential
Goldman Hodgkin Katz (GHK) Equation:
p K [K]o  p Na [Na]o  p Cl [Cl]o  p Ca [Ca]o
Vm  60 log10
p K [K]i  p Na [Na]i  p Cl [Cl]i  p Ca [Ca]i
P = permeability to ion current
 Normal High Potassium
Ion Extracellular Intracellular Extracellular Intracellular
Na+ 117 30 114 29
K+ 3 90 6 91
Cl- 120 4 120 7.9
A- 0 116 0 112.1
Relative Volume 1 1.035
Equillibrium potential z Ex
Na+ 1 35 1 36
K+ 1 -89 1 -71
Cl- -1 -89 -1 -71
A-
Membrane Potential -85 mV -68 mV

Normal Low Chloride

Ion Extracellular Intracellular Extracellular Intracellular
Na+ 117 30 117 30.5
K+ 3 90 3 89.5
Cl- 120 4 60 2
A- 0 116 60 118
Relative Volume 1 0.98
Equillibrium potential z Ex
Na+ 1 35 1 35
K+ 1 -89 1 -88
Cl- -1 -89 -1 -89
A-
Membrane Potential -85 mV -85 mV
Nerve Cells
Nerve Cell Anatomy
 Recording Nerve Activity
-85 mV
0

-V+
+ + ---- - + + + + + +
- - ++++- - - - - - - - - -

Vm

time
stimulus
Stuart GJ, Sakmann B. Active propagation of somatic action potentials into neocortical pyramidal cell dendrites.
Nature. 1994 Jan 6;367(6458):69-72. PMID: 8107777.
Characteristics of Action Potentials
• Stereotypical size and shape
• Propagation
• All-or-none response
Vm (mV) +35

-70
-90
Time (msec)
Stimulus
 Action Potentials
• Depolarization V (mV) +35
m

• Hyperpolarization 0

• Inward Current
• Outward Current -70
• Threshold -90
Time (msec)
• Overshoot Stimulus

• Undershoot (hyperpolarizing afterpotential)

• Refractory period
 Ionic basis of the Action Potential
1.Resting membrane potential
2.Upstroke of the action potential
3.Repolarization
4.Hyperpolarizing afterpotential
• These steps are mediated by the collective action of
specialized channels acting together
• The action potential is the summed membrane
potential of ion fluxes generated by all of the channels
over the duration of the impulse, as it propagates down
the cell (axon) membrane
 Gated Channels
Rest

+++

---

Ligand Gated Voltage Gated

 Gate Channels
Upstroke (sub threshold)

Na+

+++

---++

Ligand Gated Voltage Gated

 Gated Channels
Upstroke (breakthrough threshold)

Na+

-----

++++

Ligand Gated Voltage Gated

 Gated Channels
Upstroke (breakthrough threshold)

Na+

-- ++

++ - -

Ligand Gated Voltage Gated K+

 Gated Channels
Repolarization + overshoot

+ ++ +

----

Ligand Gated Voltage Gated K+

 Gated Channels
Rest

+++

---

Ligand Gated Voltage Gated

 Generation of the Action Potential
extracellular
environment cell
- membrane
intracellular environment of the [Na+] [K+] 70mv
nerve
cell
membrane

This ion inbalance is maintained by the Na+-K+ ATPase pump.

The intracellular side of the membrane is ~70mv lower in
potential that the extracellular side.

Action Potential
+ +
K+ gate Na /K pump
0
opening operating
potential
in Na + gate
millivolts
opening resting state
-70 The action potential is
propagated down the
length of a nerve cell.

time
 Refractory Period
Na Equilibrium potential Absolute Relative
+65

Vm (mV) +35

0 Inward Na+ Current

Outward K+ Current

Resting Membrane
potential
-70
K Equilibrium potential

-90
1.0 2.0 Time (msec)
 Myelinated Axons
• Oligodendrocytes and Schwann cells
• Saltatory nerve conduction
• Spinal Cord Injury
• Demyelinating neuropathy
myelinated nerve cell (Schwann cell)
unmyelinated nerve cell
node of
Schwann Ranvier
cell

myelinated nerve cell saltatory conductance

node to node
Schwann cells in the CNS
Oligodendrocite cells in the PNS
 The Synapse
• A junction between cells allowing transmission
of information carried by action potential
• Electrical and chemical synapses
• Nerve – Nerve; Neuromuscular synapes, etc.
• Presynaptic potential
• Excitatory post synaptic potential
• Inhibitory post synaptic potential
 AP

axon

synaptic vesicles

presynaptic membrane
synapse
postsynaptic membrane

postsynaptic receptors
direct ion channels
 Action Potentials Code Information
Phasic Receptor Tonic Receptor
(rapidly adapting) (slowly adapting)

Stimulus

Receptor

Nerve
 A Simple Reflex
• Knee jerk, pain
– Simple stereotypical response
– Does not require central processing
– Integrates external stimuli and appropriate
response
• How does this give rise to more complex
phenomena?
 Information

Sensory Input Summation

Motor Output