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UNITII

TextbookofMedicalPhysiology,11thEdition

Chapter5:
MembranePotentialsandActionPotentials
SlidesbyThomasH.Adair,PhD

GUYTON & HALL


Copyright2006byElsevier,Inc.

MolecularGradients
inside

outside

(in mM)

(in mM)

Na+
K+
Mg2+
Ca2+
H+
HCO3ClSO42PO3-

14
140
0.5
10-4
(pH 7.2)
10
5-15
2
75

protein

40

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142
4
1-2
1-2
(pH 7.4)
28
110
1
4
5

ActiveTransport
inside

outside

Na

Na+

ATP

K+

3 Na+
2 K+
ADP

Remember: sodium is
pumped out of the cell,
potassium is pumped in...

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SimpleDiffusion
inside

Na+

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outside

K+

Na

MembranePotential(Vm):

- charge difference across the membrane -

inside

Na+

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outside
how can passive
diffusion of potassium
and sodium lead to
development of
negative membrane
potential?

K+

Na

SimplestCaseScenario:
inside

outside

If a membrane were permeable


to only K+ then

K+

K+ would diffuse down its


concentration gradient until the
electrical potential across the
membrane countered diffusion.

Copyright2006byElsevier,Inc.

SimplestCaseScenario:
inside

outside

If a membrane were permeable


to only K+ then

K+

The electrical potential that


counters net diffusion of K+ is
called the K+ equilibrium potential
(EK).

Copyright2006byElsevier,Inc.

ThePotassiumNernstPotential
also called the equilibrium potential

EK =

Ki
61 log
Ko

Example: If Ko = 5 mM and Ki = 140 mM


EK = -61 log(140/4)
EK = -61 log(35)
EK = -94 mV

So, if the membrane were permeable only to K+,


Vm would be -94 mV

Copyright2006byElsevier,Inc.

SimplestCaseScenario:
If a membrane were permeable
to only Na+ then
Na+ would diffuse down its
concentration gradient until potential
across the membrane countered
diffusion.

inside

Na+

Na+

The electrical potential that counters


net diffusion of Na+ is called the Na+
equilibrium potential (ENa).

Copyright2006byElsevier,Inc.

outside

TheSodiumNernstPotential
EK =

Nai
61 log
Nao

Example: If Nao = 142 mM and Nai = 14 mM


EK = -61 log(14/142)
EK = -61 log(0.1)
EK = +61 mV

So, if the membrane were permeable only to Na+,


Vm would be +61 mV

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RestingMembranePotential

Vm -90 to -70
0 mV
ENa +61

EK -94

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Why is Vm so close to EK?


Ans. The membrane is far
more permeable to K than
Na..

TheGoldmanHodgkinKatzEquation

(also called the Goldman Field Equation)

Calculates Vm when more than one ion is involved.

p'K [ K ]o p' Na [ Na ]o p'Cl [Cl ]i

Vm 61. log

p'K [ K ]i p'Na [ Na ]i p'Cl [Cl ]o

or

p'K [ K ]i p' Na [ Na ]i p'Cl [Cl ]o

Vm -61. log

p'K [ K ]o p'Na [ Na ]o p'Cl [Cl ]i

Copyright2006byElsevier,Inc.

NOTE:
P = permeability

TheGoldmanHodgkinKatzEquation
Take home message
Therestingmembranepotentialisclosesttothe
equilibriumpotentialfortheionwiththehighest
permeability!

Copyright2006byElsevier,Inc.

RestingMembranePotentialSummary

Figure 5-5; Guyton & Hall

Copyright2006byElsevier,Inc.

Restingandactionpotentials

Recallthatcells:

containhighaK concentration
havemembranesthatareessentially
permeabletoK+atrest
+

Membraneelectricalpotentialdifference
(membranepotential)isgeneratedby
diffusionofK+ionsandchargeseparation
measuredinmV(=1/1000thof1V)
typicallyrestingmembranepotentialsin
neuronsare70to90mV

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-80
mV
0 mV

Voltmeter

+
+
+

+
+

+
+

+
+

Propertiesofactionpotentials

areinitiatedbydepolarization
actionpotentialscanbeinducedinnerveand
musclebyextrinsic(percutaneous)stimulation
haveconstantamplitude
APsdonotsummateinformationiscodedby
frequencynotamplitude.
haveconstantconductionvelocity
Trueforgivenfiber.Fiberswithlargediameter
conductfasterthansmallfibers.Asageneral
rule:
myelinatedfiberdiameter(inmm)x4.5=
velocityinm/s.
Squarerootofunmyelinatedfiberdiameter

=velocityinm/s

Copyright2006byElsevier,Inc.

0
mV

threshold

-70
Stimulus

areallornoneevents
thresholdvoltage(usually15mVpositiveto
restingpotential)

+60

75

Velocity (m/s)

Actionpotentials:

Myelinated
(cat)

50

non-myelinated
(squid)

25
0
0
0

12

400
800
Fiber diameter (m)

15

TheAPmembranepermeability

Afterhyperpolarizationofmembranefollowingan
actionpotential:
notalwaysseen!
ThereisincreasedK+conductance
duetodelayedclosureofK+channels

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upstro
k

resting potential
-90
1 ms

Number of open channels

Kpermeabilityincreases
duetoopeningofK+channels
mem.potentialapproachesEK

(mV)

ok e

Duringthedownstrokeofanactionpotential:
Napermeabilitydecreases
duetoinactivationofNa+channels

nstr

Duringtheupstrokeofanactionpotential:
Napermeabilityincreases
duetoopeningofNa+channels
memb.potentialapproachesENa

ENa

do w

+61

EK
Membrane
hyperpolarized

Na+ channels
K+ channels

Ionchannels

closed

Ionchannelsstructure
proteinsthatspanthemembrane
havewaterfilledchannelthatrunsthrough
protein

Ionchannelproperties

re
po
la
riz
at
io
n

de
po
la
riz
at
io
n

Haveconductingstatesandnon
conductingstates
transitionbetweenstates=gating

inactivation
open

inactivated

channelsgateinresponseto:
changesinmembranepotential(usuallydepolarization)
voltagegatedchannels.Actionpotentialpropagationreliesonvoltagegatedchannels
occupationofreceptor
ligandgatedorreceptoroperatedchannels(ROCs).Theseinitiateactionpotentials
mechanicalforces
mechanosensitivechannelsimportantforhearing.

Copyright2006byElsevier,Inc.

Propagation:
Opening of Na+ channels generates local current circuit that
depolarizes adjacent membrane, opening more Na+ channels
Rest
Stimulated
(local depolarization)
Propagation
(current spread)

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Signal Transmission:
Myelination
Schwann cells surround
the nerve axon forming a
myelin sheath
Sphingomyelin decreases
membrane capacitance and
ion flow 5,000-fold
Sheath is interrupted
every 1-3 mm : node of
Ranvier

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Figure 5-16; Guyton & Hall

Saltatory Conduction
APs only occur at the nodes (Na
channels concentrated here!)

increased velocity
energy conservation

Figure 5-17; Guyton & Hall


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Conductionvelocity
nonmyelinatedvsmyelinated

nonmyelinated

myelinated

Copyright2006byElsevier,Inc.

MultipleSclerosis

- MS is an immune-mediated
inflammatory demyelinating
disease of the CNS - About 1 person per 1000 in
US is thought to have the
disease - The female-to-male
ratio is 2:1 - whites of northern
European descent have the
highest incidence

http://www.emedicine.com/pmr/topic82.htm
Copyright2006byElsevier,Inc.

Patients have a difficult time


describing their symptoms. Patients
may present with paresthesias of a
hand that resolves, followed in a
couple of months by weakness in a leg
or visual disturbances. Patients
frequently do not bring these
complaints to their doctors because
they resolve. Eventually, the resolution
of the neurologic deficits is incomplete
or their occurrence is too frequent, and
the diagnostic dilemma begins.