Membrane Potentials - Ch. 5 - [Download PPT Powerpoint]

U N I T II

Textbook of Medical Physiology, 11th Edition

GUYTON & HALL

Chapter 5:Membrane Potentials and Action Potentials

Slides by Thomas H. Adair, PhD

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

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...

Simple Diffusioninside outside

K+ K+

Na+Na+

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?

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.

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

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

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.

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

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..

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

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…

Resting Membrane Potential Summary

Figure 5-5; Guyton & Hall

• 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 +

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.

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

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

Propagation:

Rest

Opening of Na+ channels generates local current circuit that depolarizes adjacent membrane, opening more Na+ channels…

Stimulated(local depolarization)

Propagation(current spread)

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

Saltatory Conduction• AP’s only occur at the nodes (Na channels concentrated here!)• increased velocity• energy conservation

Figure 5-17; Guyton & Hall

Conduction velocity

non-myelinatednon-myelinated

myelinatedmyelinated

- non-myelinated vs myelinated -- non-myelinated vs myelinated -

- 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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