U N I T II
Textbook of Medical Physiology, 11th Edition
GUYTON & HALL
Copyright © 2006 by Elsevier, Inc.
Chapter 5:Membrane Potentials and Action Potentials
Slides by Thomas H. Adair, PhD
Copyright © 2006 by Elsevier, Inc.
Molecular Gradients
Na+
K+
Mg2+
Ca2+
H+
HCO3-
Cl-
SO42-
PO3-
protein
inside(in mM)
141400.510-4
(pH 7.2)10
5-152
75
40
outside(in mM)
14241-21-2(pH 7.4)2811014
5
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ATP
3 Na+
2 K+
ADP
Active Transport
K+ Na+
Na+ K+
inside outside
Remember: sodium is pumped out of the cell, potassium is pumped in...
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Simple Diffusioninside outside
K+ K+
Na+Na+
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Membrane Potential (Vm): - charge difference across the membrane -
K+
Na+
K+
Na+
inside outside…how can passive diffusion of potassium and sodium lead to development of negative membrane potential?
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Simplest Case Scenario:
If a membrane were permeable to only K+ then…
inside outside
K+ K+
K+ would diffuse down its concentration gradient until the electrical potential across the membrane countered diffusion.
Copyright © 2006 by Elsevier, Inc.
Simplest Case Scenario:
K+ K+
If a membrane were permeable to only K+ then…
The electrical potential that counters net diffusion of K+ is called the K+ equilibrium potential (EK).
inside outside
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The Potassium Nernst Potential
Example: If Ko = 5 mM and Ki = 140 mM
EK = -61 log(140/4)
EK = -61 log(35)
EK = -94 mV
EK = 61 log
Ki
Ko
So, if the membrane were permeable only to K+, Vm would be -94 mV
…also called the equilibrium potential
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Simplest Case Scenario:
Na+Na+
If a membrane were permeable to only Na+ then…
The electrical potential that counters net diffusion of Na+ is called the Na+ equilibrium potential (ENa).
inside outside
Na+ would diffuse down its concentration gradient until potential across the membrane countered diffusion.
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The Sodium Nernst Potential
Example: If Nao = 142 mM and Nai = 14 mM
EK = -61 log(14/142)
EK = -61 log(0.1)
EK = +61 mV
EK = 61 log
Nai
Nao
So, if the membrane were permeable only to Na+, Vm would be +61 mV
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Resting Membrane Potential
0 mV
EK -94 ENa +61
Vm -90 to -70
Why is Vm so close to EK?Ans. The membrane is far more permeable to K than Na..
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The Goldman-Hodgkin-Katz Equation (also called the Goldman Field Equation)
Calculates Vm when more than one ion is involved.
oCliNaiK
iCloNaoKm
ClpNapKp
ClpNapKpV
]['][']['
]['][']['log.
61
NOTE:P’ = permeability
iCloNaoK
oCliNaiKm
ClpNapKp
ClpNapKpV
]['][']['
]['][']['log.
-61
or
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The Goldman-Hodgkin-Katz Equation
The resting membrane potential is closest to the equilibrium potential for the ion with the highest permeability!
Take home message…
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Resting Membrane Potential Summary
Figure 5-5; Guyton & Hall
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• Recall that cells: – contain high a K+ concentration
– have membranes that are essentially permeable to K+ at rest
• Membrane electrical potential difference (membrane potential) is generated by diffusion of K+ ions and charge separation
– measured in mV (=1/1000th of 1V)
– typically resting membrane potentials in neurons are -70 to 90 mV
Resting and action potentials
+
+
+
++ +
+
+
+
+ +
–
––
– –––
–––
–
Voltmeter
– +0 mV-80 mV +
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Properties of action potentials• Action potentials:
are all-or-none events threshold voltage (usually 15 mV positive to
resting potential) threshold
-70
+60
mV
Stim
ulus
0
non-myelinated(squid)
0 800400
have constant conduction velocity True for given fiber. Fibers with large diameter
conduct faster than small fibers. As a general rule:
myelinated fiber diameter (in mm) x 4.5 = velocity in m/s.
Square root of unmyelinated fiber diameter = velocity in m/s Fiber diameter (m)
Vel
ocity
(m
/s)
0 3 6 9
Myelinated(cat)
12
75
15
50
25
0
are initiated by depolarization action potentials can be induced in nerve and
muscle by extrinsic (percutaneous) stimulation have constant amplitude
APs do not summate - information is coded by frequency not amplitude.
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The AP - membrane permeability
• During the upstroke of an action potential: Na permeability increases
due to opening of Na+ channels memb. potential approaches ENa
Num
ber
of o
pen
chan
nel s
Na+ channels
upst
roke
K permeability increases due to opening of K+ channels
mem. potential approaches EK
downstroke
• After hyperpolarization of membrane following an action potential:
Membranehyperpolarized
resting potential
K+ channels
not always seen! There is increased K+ conductance
due to delayed closure of K+ channels
• During the downstroke of an action potential: Na permeability decreases
due to inactivation of Na+ channels 1 ms
+61
0
(mV)
-90
ENa
EK
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Ion channels• Ion channels - structure
proteins that span the membrane have water filled channel that runs through
protein
• Ion channel - properties Have conducting states and non-
conducting states transition between states = ‘gating’
• channels ‘gate’ in response to: changes in membrane potential (usually depolarization)
voltage-gated channels. Action potential propagation relies on voltage-gated channels occupation of receptor
ligand-gated or receptor operated channels (ROCs). These initiate action potentials mechanical forces
mechanosensitive channels - important for hearing.
openopen
inactivationinactivation
inactivatedinactivated
closedclosed
depo
lariza
tion
depo
lariza
tion repolarization
repolarization
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Propagation:
Rest
Opening of Na+ channels generates local current circuit that depolarizes adjacent membrane, opening more Na+ channels…
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
Figure 5-16; Guyton & Hall
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Saltatory Conduction• AP’s only occur at the nodes (Na channels concentrated here!)• increased velocity• energy conservation
Figure 5-17; Guyton & Hall
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Conduction velocity
non-myelinatednon-myelinated
myelinatedmyelinated
- non-myelinated vs myelinated -- non-myelinated vs myelinated -
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- MS is an immune-mediated inflammatory demyelinating disease of the CNS -
Multiple Sclerosis
- About 1 person per 1000 in US is thought to have the disease - The female-to-male The female-to-male ratio is 2:1 - whites of northern ratio is 2:1 - whites of northern European descent have the European descent have the highest incidencehighest incidence
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.
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