Elina_Kaplan_Physiology Ionic Equilibrium And Resting Membrane Potential

Front 1

ELECTROCHEMICAL POTENTIAL
Membrane Conductance
Definition

Back 1

Membrane conductance refers to the number of channels that are open in a membrane. For
example, Na I conductance is proportional to the number of open channels that will allow the
Na+to pass through the membrane. It does not indicate if there will be a net diffusion of ions
through the channels

Front 2

Membrane Conductance
If condnctance is increasing what will be with channels and vise versa

Back 2

If condnctance is increasing, channels are opening, and if conductance is decreasing, channels
are closing. .
The rate at which ions move across a membrane depends on the number of open channels and
the net force

Front 3

Membrane Conductance
Channels are classified into three main groups:.....

Back 3

Ungated channels
Voltage-gated channels:
Ligand-gated channels:

Front 4

Membrane Conductan Ungated channelsce

Back 4

Because these channels have no gates, they arc always open. For
example, all cells possess ungated potassium channels. This means there will be a net
flux of potassium ions through these channels unless potassium is at equilibrium.

Front 5

Membrane Conductan Voltage-gated channels:

Back 5

Voltage-gated channels: In these channels, the gates open and/or close in response to
a membrane voltage change. For example, many excitable cells possess voltage-gated
sodium channels. The channels are closed under resting conditions, but membrane
depolarization causes them to quickly open and then quickly close

Front 6

Membrane Conductan Ligand-gated channels

Back 6

Ligand-gated channels: The channel complex includes a receptor to a specific substance
(ligand). It is the interaction of the ligand with the receptor that regulates the
opening and closing of the channel. For example, post-junctional membranes of
chemical synapses possess ligand-gated channels, and transmission depends on the
interaction of the transmitter and the ligand-gated channel

Front 7

Concentration force is determined by...

Back 7

Concentration force
This is determined by the concentration difference across the membrane.
The greater the concentration difference, the greater the concentration force.

Front 8

Electrical force is determined by...

Back 8

Electrical force
The size of this force is determined by the electrical difference across the membrane (usually
measured in millivolts [rnV]),

Front 9

Application ofthe Nernst equation

Back 9

Application ofthe Nernst equation
If the membrane potential (Em) has been measured or given in an example and the equilibrium
potential of an ion (Ex) calculated by using the Nernst equation, the following conclusions
can be drawn:

Front 10

The difference between Ex and the measured membrane potential (Ern) represents .....

Back 10

The difference between Exand the measured membrane potential (Ern) represents the net force
on the ion

Front 11

The Nernst equation
The rate at which an ion will diffuse across a membrane is directly proportional....

Back 11

The rate at which an ion will diffuse across a membrane is directly proportional to the
net force and membrane conductance to that particular ion. Note that as an ion diffuses
and the membrane potential approaches the equilibrium potential for that ion,
the net force on the ion decreases. When the membrane potential reaches the ion's
equilibrium potential, the net force is zero.

Front 12

RESTING MEMBRANE POTENTIAL
ECl- is?

Back 12

ECl- = -90 mV

Front 13

RESTING MEMBRANE POTENTIAL
E K' is?

Back 13

EK' =-95 mV

Front 14

RESTING MEMBRANE POTENTIAL
E Na.' is?

Back 14

ENa.' = +45 mV

Front 15

RESTING MEMBRANE POTENTIAL
Important Points Regarding (CL)

Back 15

Becausethe measured membrane potential and the calculated equilibrium potential are the same
in magnitude and charge, the chloride ions are at equilibrium.

Front 16

RESTING MEMBRANE POTENTIAL
Important Points Regarding K+

Back 16

The potassium ions are not at equilibrium. The net force on the potassium ions is 15 mY

Front 17

RESTING MEMBRANE POTENTIAL
Increasing potassium conductance приведет к.....

Back 17

Increasing potassium conductance will accelerate the efflux of potassium ions and hyperpolarize
the cell

Front 18

RESTING MEMBRANE POTENTIAL Decreased extracellular potassium ions will accelerate

Back 18

Decreased extracellular potassium ions will accelerate the efflux of the potassium ions, the net
result of which will be hyperpolarization.

Front 19

RESTING MEMBRANE POTENTIAL
a cell's resting membrane potential is very sensitive to changes in....

Back 19

a cell's resting membrane potential is very sensitive to changes in the extracellular
potassium ion concentration.

Front 20

RESTING MEMBRANE POTENTIALImportant Points Regarding Na+

Back 20

The sodium ions are not at equilibrium. The net force on the sodium ions is 135 mY.This is
considered a large force; therefore, the sodium ions are a long way from equilibrium.

Front 21

Resting Membrane Potential
Important Points Regarding Na"
An increase in membrane conductance to sodium ions will produce

Back 21

An increase in membrane conductance to sodium ions will produce an influx of sodium ions
and depolarization.

Front 22

Resting Membrane Potential
Important Points Regarding Na"
a cell's resting membrane potential to changes in extracellular sodium is ....

Back 22

is not sensitive

Front 23

Resting Membrane Potential DEpolarization:

Back 23

DEpolarization: The negative intracellular potential moves toward zero (becomes more posi~);
e.g., Na+ influx depolarizes a cell

Front 24

Resting Membrane Potential hyperpolarization:

Back 24

lIfperpolarization: The negative intracellular potential becomes more negative, e.g., increased
r- effluxfrom a ce

Front 25

Resting Membrane Potentia transmembrane potential:

Back 25

'bansmembrane potential: Potential difference across a cell membrane (sign not involved). If
themembrane potential is -70 mY,the transmembrane potential is 70 mY. As a cell undergoes
dq>olarization and the membrane potential approaches zero, the transmembrane potential
decreases in magnitude

Front 26

THE ACTION POTENTIAL Conduction of nerve signals is done by a rapid membrane depolarization that changes is

Back 26

Conduction of nerve signals is done by a rapid membrane depolarization that changes the
normal resting negative potential to a positive potential.

Front 27

THE ACTION POTENTIAL Ungated Potassium Channels

Back 27

Ungated Potassium Channels
These channels are alwaysopen, and unless the membrane potential reaches the potassiwn equilibrium
potential (- -95 rnV), a potassium ion efflux is maintained through these channels.

Front 28

THE ACTION POTENTIAL Voltage-Gated Sodium Channels (Fast Na+ Channel}

Back 28

These channels are closed under resting conditions. Membrane depolarization is the signal that
causes these channels to quickly open and then dose. This time-dependent property is called
inactivation. Once they dose, they will not respond to a second stimulus until the cell almost
completely repolarizes. Closure of sodium channels is essential for the rapid repolarization
phase of the action potential.

Front 29

THE ACTION POTENTIAL Voltage-gated sodium channels are required for....

Back 29

Voltage-gated sodium channels are required for the depolarization phase and thus the generation
of an action potential in neurons and skeletal muscle. Preventing the opening of these
channels in response to depolarization will prevent the development of an action potential.

Front 30

THE ACTION POTENTIAL Voltage-Gated Potassium Channels

Back 30

These channels are dosed under resting conditions. membrane depolarization is the signal that causes these channels to open. However,
they open more slowly than the sodium channels, and thus opening peaks later during the
action potential. These channels assist the rapid repolarization phase. Preventing their opening
slows repolarization

Front 31

Depolarization Phase
initial depolarization is

Back 31

Initial depolarization is the stimulus that causes the opening of the voltage-gated sodium channels
(open fast, dose fast),

Front 32

Depolarization Phase
pening of the sodium channels increases ....

Back 32

Opening of the sodium channels increases the membrane conductance to sodium ion, permitting
a rapid sodium ion influx.

Front 33

Depolarization Phase

Back 33

Sodium channels are opening throughout depolarization, and peak sodium conductance is not
reached until just before the peak of the action potential. Even though peak sodium conductance
represents a situation with a large number of open sodium channels, influx is minimal
because the membrane potential is dose to the sodium ion equilibrium potential.

Front 34

Repolarization

Back 34

During early repolarization, the voltage-gated sodium channels are rapidly closing. This eliminates
a sodium ion flux across the membrane.

Front 35

Absolute refractory period (functional refractory period)

Back 35

Absolute refractory period (functional refractory period)
The absolute refractory period is that period during which no matter how strong the stimulus,
it cannot induce a second action potential.

Front 36

Relative refractory period

Back 36

Relative refractory period
The relative refractory period is that period during which a greater than norma] stimulus is
required to induce a second action potential.

Front 37

Action Potential
Several factors determine the velocity of the action potential

Back 37

Size of the action potential:
Cell diameter:
Myelination
:Demyelination

Front 38

Action Potential
Size of the action potential:

Back 38

Size of the action potential: The greater the size and rate of depolarization of the
action potential generated, the faster it moves across the surface of the cell.

Front 39

Action Potential
Cell diameter:

Back 39

Cell diameter: The greater the cell diameter, the greater the conduction velocity. A
greater cross-sectional surface area reduces the electrical resistance.

Front 40

Action Potential
Myelination:

Back 40

Myelination: Myelin provides a greater electrical resistance across the cell membrane.
The myelination is interrupted at the nodes of Ranvier. With myelin surrounding
the membrane, less of the electrical signal is lost during transmission. In other words
less current leaks to ground. The signal is conducted with minimal decrement and at
greater speed from node to node. It is at the nodes where the sodium and potassium
channels are concentrated. The movement of the action potential from node to node
is called salutatory conduction.

Front 41

Action Potential
Demyelination

Back 41

Demyelination (e.g., multiple sclerosis, Guillain-Barre syndrome): This would decrease
the amplitude of the action potential as it travels from node to node. If the action
potential arrives below a certain magnitude, another action potential may not be generated
and transmission is blocked.

Front 42

ELECTRICAL SYNAPSES

Back 42

ELECTRICAL SYNAPSES
• Action potential is transmitted from one ceIl to another by the direct flow of current.
• Conduction can occur in both directions, and there is essentially no synaptic delay.
• Cells with electrical synapses are joined by gap junctions.
• Cardiac cells and single-unit smooth muscle cells and some neurons have electrical
synapses.

Front 43

Summary of Events Occurring During Neuromuscular Transmission

Back 43

-opens voltage-gated calcium channels
-an influx of extracellular ca2+ into
the axon terminal.
-rise in intracellular free Ca2+ causes the release of acetylcholine from synaptic vesicles
into the synaptic cleft.
-Diffusion of acetylcholine to the postjunctional membrane
-Combination of acetylcholine with cholinergic, nicotinic receptors
-Opening of ligand-dependent channels results in an increased conductance to Na" and K+.
-Influx ofNa+ causes local depolarization
-depolarization of areas of muscle membrane adjacent to the end
plate,

Front 44

SYNAPSES BETWEEN NEURONS

Back 44

-Synapses are located on the cell body and dendrites.
-The cell membrane in these regions is specialized for chemical sensitivity and thus
dominated by ligand-dependent channels, producing excitatory postsynaptic potentials
(EPSPs) and inhibitory postsynaptic potentials (IPSPs) in response to the different
transmitters.
These voltage changes are conducted electronically along the dendritic and cell body
membranes to the axon hillock-initial segment region.
• The closer the synapse is to this region, the greater its influence in determining whether
an action potential is generated.
The axon hillock-initial segment region has a particularly low threshold (voltage gated
channels).
• If the sum of all the inputs reaches threshold, an action potential will be generated
and conducted along the axon to the nerve terminals.
• Termination of the action of acetylcholine on the postsynaptic membrane is mainly by
enzymatic destruction, whereas with other transmitters it is by reuptake by the presynaptic
membrane and/or diffusion away from the site of action.

Front 45

Characteristics of EPSPs ITransient Depolarizations)

Back 45

• They are excitatory because Em moves closer to its threshold.
• Produced as a result of an increase in conductance to Na" and K+
The Na+ influx causes depolarization.
The EPSPs at synapses between neurons are similar to the EPPs at neuromuscular
junctions.
• Transmitters that generate EP$Ps would include acetylcholine, glutamate, and aspartate.

Front 46

Characteristics of IPSPs ITransient Hyperpolarizations)

Back 46

• They are inhibitory because Emmoves farther away from its threshold.
• Produced at least in some cases by an increased conductance to CJThe
cr influx causes hyperpolarization.
Transmitters that generate IPSPs would include glycine and GABA.

Front 47

Electrical Activity of the Heart
Ungated Potassium Channels

Back 47

Ungated Potassium Channels
Always open and unless the membrane potential reaches the potassium equilibrium potential
(- -94 mY), a potassium flux (efflux) is maintained through these channel

Front 48

Electrical Activity of the Heart
Voltage-Gated Sodium Channels

Back 48

• Membrane depolarization is the signal that causes these channels to quickly open and
then close.
Because they open and close quickly,they are sometimes referred to as fast channels.
These channels have the same characteristics as the voltage-gated sodium channels in
the neuron axon.
• Once dosed, they will not respond to a second stimulus until the cell rcpolarizes.

Front 49

Electrical Activity of the Heart
Voltage-Gated Calcium Channels

Back 49

• Closed under resting conditions, when the membrane potential is highly negative.
Depolarization is the signal that causes these channels to open, but they open more
slowly than the sodium channels.
Consequently, they are sometimes called the slow channels. They are also called
L-type, for long-acting channels.• Because they allow sodium as well as calcium to pass, the slow calcium-sodium channel
is also appropriate terminology.
The calcium entering the cell through these channels will participate in contraction
and will also he involved in the release of additional calcium from the sarcoplasmic
reticulum.
If the fast channels fail to open, depolarization occurs via the entrance of calcium
through these channels. In this situation, the action potential of fast response cells will
resemble that of slow response cells

Front 50

Electrical Activity of the Heart
Inward rectifying channels, iK

Back 50

Inward rectifying channels, iK1
These get their name from the fact that in some experimental conditions, an inward
potassium current can occur.
Open under resting conditions (negative membrane potentials), depolarization is the
signal to close these channels.
They will be dosing during the depolarization phase and will be closed during the
main part of the plateau phase.
They reopen again during repolarization, Thus, potassium conductance is exceptionally
high under resting conditions, decreases during depolarization, is at a minimum
during the plateau phase, and increases hack toward the high resting level during
repolarization.
Low potassium conductance during the plateau phase is extremely important; when
the cell is depolarized, there is no potential to hold potassium inside the cell, so there
would be excessiveloss of potassium from the cell during the plateau.

Front 51

Delayed rectifying channels, iK

Back 51

Delayed rectifying channels, iK
• Control is more like potassium channels in nerves; the iK channel opens with depolarization
and closes when the cell is repoJarized.
• However, they are very slow to open (delayed). They typically open late in the plateau
phase of the action potential to speed repolarization.
• They close very slowly. They remain open into the resting potential and contribute to
the extended period of the relative refractory period during resting potential.

Front 52

ACTION POTENTIAL OF AVENTRICULAR FIBER (FAST fibers

Back 52

Fast fibers have functioning fast channels. Depolarization will be rapid and the action potential
spreads very quickly across the surface of the celL Fast fibers include ventricular fibers, atrial
fibers, and Purkinje fibers.

Front 53

ACTION POTENTIAL OF AVENTRICULAR FIBER slow fibers

Back 53

Slow fibers lack functioning fast channels. As a consequence, depolarization is slower and the
action potential travels more slowly across the surface of the cell. Slow fibers include the SA and
AV nodal fibers. Fast fibers can be converted into slow fibers. For example, in ischemic tissue,
potassium in the surrounding interstitium rises. The Jess negative resting membrane potential
can convert a normally fast fiber into a slow fiber. Conduction is more likely to be blocked in a
slow fiber.

Front 54

Ionic Basis of the Action Potential
Phase 0

Back 54

Phase 0
• Fast channels open, i gNa' Sodium influx then causes depolarization.
• The channels open and dose quickly, and they have dosed by the time the main part
of the plateau phase is entered.

Front 55

Ionic Basis of the Action Potential
Phase 1

Back 55

Phase 1
This slight repolarization is due to a transient potassium current and the dosing of
the sodium channels. Originally it was thought that CI was involved, though we now
know that is not the case.
Subendocardial fibers lack a phase 1.

Front 56

Ionic Basis of the Action Potential
Phase 2

Back 56

Phase 2
• L-type Ca2+ channels are open, gCa t permitting a calcium influx.
Voltage-gated potassium channels, the iKI, are closed; gK -1. compared with resting
membrane.
Potassium efflux continues through the ungated potassium channels and possibly
other channels.
• If voltage-gated potassium channels did not close during depolarization, early repolarization
would occur, preventing the full development of the plateau phase.
• The development of the plateau phase is dependent on the closing of voltage-gated
potassium channels.
• Calcium channel antagonists shorten the plateau.
• Potassium channel antagonists lengthen the plateau.

Front 57

Ionic Basis of the Action Potential
Phase 3

Back 57

Phase 3
L-type Ca2+ channels close,gCa -1.; this eliminates any influx through these channels.
Voltage-gatedpotassium channels, the delayed rectifier iK, then the iK j are opening, gK T.
Becausewe are a long way from the potassium equilibrium potential and conductance to
potassium is increasing, a large potassium efflux begins, and the cell quickly repolarizes.
If the voltage-gated potassium channels did not open, the cell would still repolarize
but more slowly,because of closure of calcium channels and potassium efflux through
the ungated potassium channels.

Front 58

Ionic Basis of the Action Potential
Phase 4

Back 58

Phase 4
gK high; voltage-gated and ungated potassium channels open. The delayed rectifiers,
iK, gradually close but are responsible for the relative refractory period during early
phase 4.