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MSK Exam 2 > Physiology of Membrane Potentials > Flashcards

Physiology of Membrane Potentials Flashcards

1
Q

Intracellular Fluid Composition (25L)
[Na+] =
[K+] =
[Cl-] =
[Protein] =

A

[Na+] = 15 mM
[K+] = 120 mM
[Cl-] = 20 mM
[Protein] = 3 mM

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2
Q

Interstitial Fluid (13L)
[Na+] =
[K+] =
[Cl-] =
[Protein] =

A

[Na+] = 145 mM
[K+] = 4.2 mM
[Cl-] = 113 mM
[Protein] = 0 mM

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3
Q

Blood Plasma (3L)
[Na+] =
[K+] =
[Cl-] =
[Protein] =

A

[Na+] = 142 mM
[K+] = 4 mM
[Cl-] = 103 mM
[Protein] = 1 mM

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4
Q

What is the osmolarity of interstitial fluid, interstitial fluid, and blood plasma?

A

All have the same osmolarity of 285 mOsM

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5
Q

What makes-up Extracellular Fluid?

A
  • Interstitial Fluid
  • Blood Plasma
  • Transcellular Fluid (ex. fluid present in epithelial cells)
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6
Q

ICF is high in __ but low in __ and __

A

High in K+ but low in Na+ and Cl-

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7
Q

ECF is high in __ and __ but low in __

A

High in Na+ and Cl- but low in K+

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8
Q

The gates on gated ion channels are controlled by sensors that can respond to:

A
  • Ligand
  • Voltage
  • Post-translational modification
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9
Q

Voltage-Gated Channels

A
  • gates controlled by changes in membrane potential
  • Ex. voltage gated K+ channels, voltage gated Na+ channels
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10
Q

Ligand-Gated Channels

A
  • gates controlled by the binding of a ligand such as a NT
  • Ex. Ach receptors
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11
Q

Diffusion Potential

A
  • the potential difference generated across a membrane when an ion diffuses down its concentration gradient
  • magnitude of this depends on the size of the concentration gradient – concentration gradient is the driving force, measured in mV
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12
Q

How Equilibrium Potential is Reached
(ex. Na+ selective membrane with Na+ and Cl- ions on either side of the membrane)

A

(1) Na+ ions travel down their concentration gradient, but Cl- ions remain in one side
(2) Positive charge is now built up on one side of the membrane (one side is now positive with respect to the other side)
(3) The positive charge on one side will now prevent further movement of Na+. Electrical force drives Na+ out of the side it originally went to and back to the other side.
(4) At equilibrium, a Na+ ion moves down its concentration gradient for every Na+ ion that moves from one side to the other down its electrical gradient.
*at equilibrium there is no further change in Na conc in the two sides, and no further change in the elctrical potential

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13
Q

Equilibrium Potential

A
  • for an ion, it is determined not only by chemical forces (concentration gradient) but also by electrical forces
  • the state in which the tendency of ions to flow across a cell membrane from regions of high concentration is exactly balanced by the opposing potential difference (electric charge) across the membrane
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14
Q

What does the Nernst Equation estimate?

A

The equilibrium potential for a given ion

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15
Q

Simplified Nernst Equation

A

Ex = (61.5 mV / z) x (log [Ce]/[Ci])

z = charge of the ion
Ce = extracellular concentration for a given ion
Ci = intracellular concentration for a given ion

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16
Q

Approximate concentrations of Na+ (mEq/L or mM) in the:
(1) ECF =
(2) ICF =

A

(1) ECF = 140
(2) ICF = 14

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17
Q

Approximate concentrations of K+ (mEq/L or mM) in the:
(1) ECF =
(2) ICF =

A

(1) ECF = 4
(2) ICF = 120

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18
Q

What is the typical value of equilibrium potential for Na+ in skeletal muscle?

A

+65 mV

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19
Q

What is the typical value of equilibrium potential for K+ in skeletal muscle?

A

-95 mV

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20
Q

What is the typical value of equilibrium potential for Ca2+ in skeletal muscle?

A

+120 MV

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21
Q

What is the typical value of equilibrium potential for Cl- in skeletal muscle?

A

-90 mV

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22
Q

What does the driving force for net diffusion of ions account for?

A

Both the concentration gradient and the electrical potential across the membrane

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23
Q

What is the equation for Net Driving Force (mV)?

A

Net Driving Force (mV) = Em - Ex

Em = membrane potential (mV)
Ex = equilibrium potential for a given ion (mV)

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24
Q

What happens when the driving force is negative (Em is more negative than the Ex)?

A
  • Cation will enter the cell
  • Anion will leave the cell
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25
Q

What happens when the driving force is positive (Em is more positive than Ex)?

A
  • Cation will leave the cell
  • Anion will enter the cell
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26
Q

What happens if the driving force is zero (Em is equal to Ex)?

A
  • No net movement of the ion in either direction
27
Q

Electrical (Ionic) Current

A
  • the movement of ions between the ICF and ECF across the cell membrane
28
Q

What two things determine the ionic current?

A
  • Conductance and driving force of a given ion

Ix = Gx (Em - Ex)

Ix = ionic current (mAmp)
Gx = ionic conductance (S)
Em - Ex = driving force of a given ion (mV)

29
Q

What two factors affect the ionic current across the cell membrane?

A

(1) Different between the equilibrium potential for a given ion and the actual membrane potential (ex. the driving force = Em - Ex)
(2) Permeability of a membrane to a given ion

30
Q

If there is a large difference between Em and Ex, what is likely to happen?

A
  • large imbalance between the electrical and concentration gradients
  • large net movement of the given ion
31
Q

If the permeability of an ion is high, the ionic current at a particular value of driving force will be ___ than if the permeability was ___.

A
  • higher
  • low
32
Q

Conductance

A
  • an index of the ability of an ion to carry current across a membrane
33
Q

For a given driving force, the greater the conductance, the greater the ___ __.

A

current flow

34
Q

Two Factors that determine Membrane Potential

A
  • Concentration gradients across the cell membrane
    (Na/K ATPase largely develops and maintains the concentration gradient)
  • Relative ion permeabilities
    (ions with the highest permeabilities or conductances at rest will make the greatest contribution to the resting membrane potential)
35
Q

Goldman-Hodgkin-Katz Equation

A

Em = 61.5 log( [K]outside + b[Na]outside + c[Cl]inside / [K]inside + b[Na]inside + c[Cl]outside )

can only use ions that are permeable to the membrane in the equation

  • says that the combination of an outwardly directed K+ gradient (product of the Na/K ATPase activity) and the high permeability of the membrane to K+ makes the ICF electrically negative with respect to the ECF; however, the finite permeability of the membrane to Na and Cl (due to leak channels) prevents the membrane potential from reaching the Nernst potential for K
  • essentially this gives the relative permeability of a specific ion compared to K+ during resting state
36
Q

For neurons, there are more __ channel than any other type of ion channel open at rest

A

K+

37
Q

Roles of Na/K ATPase

A
  • Electrogenic contribution – 3 Na+ ions pumped OUT of the cell for every 2 K+ ions pumped IN the cell
  • Maintains the concentration gradient of Na and K
38
Q

What is the basis of the transient depolarization of the membrane potential that occurs due to an AP?

A

Large increase in Na+ permeability (therefore increase in conductance) due to the activation of voltage-gated Na+ channels

39
Q

Characteristics of the AP

A
  • Triggered by depolarization
  • Threshold must be reached to trigger AP (about -55 mV)
  • AP are all or nothing events
  • Propagation of APs from one site to the next is non-decremental
  • A the peak of an AP the membrane potential reverses sign becoming inside positive relative to the outside
  • After neuron fires an AP there is a brief period where it is impossible to trigger another AP (absolute refractory period)
40
Q

What is the RMP?

A

-70 mV

41
Q

Depolarizing Phase of AP

A
  • Membrane potential becomes less negative than the resting membrane potential
  • Characterized by an inward current associated with the increased conductance of Na+
  • During this phase, Na+ influx dominates
  • After threshold has been reached, depolarization becomes self-sustained, giving rise to the upstroke
42
Q

Peak of AP

A
  • Maximum amplitude (depolarization) of AP
43
Q

Overshoot of AP

A
  • membrane potential transiently overshoots zero, and the inside of the cell becomes positive with respect to the outside of the cell for a brief period of time
44
Q

Repolarization Phase of AP

A
  • The upstroke is terminated and the membrane repolarizes to the resting level (-70 mV)
45
Q

Hyperpolarization Phase of AP

A
  • Membrane potential becomes more negative than the RMP
46
Q

Positive feedback loop of Voltage-Gated Na+ Channels during AP

A
  • When membrane is depolarized, Na permeability increases, allowing more Na ions to carry positive charge into the cell; this depolarizes the cell further, causing greater increase in Na permeability and more depolarization
  • This process is explosive and continues until all Na+ channels are open and the membrane potential has been driven up to near Na Equilibrium
47
Q

What causes Em to return to rest after the AP?

A
  • Depolarization-induced increase in Na permeability is transient
  • There is a delayed, voltage-dependent increase in K+ permeability
48
Q

Effect of Depolarization on Voltage-Gated Na+ Channels

A
  • Activation gate of channel is closed when the Em is equal to or more negative than the usual RMP: prevents Na from entering the cell at the RMP
  • Inactivation gate of channel is open at RMP
  • Both gates respond to depolarization but with different speeds and in opposite directions: activation gate opens rapidly in response to depolarization, inactivation gate closes in response to depolarization but does this slowly
  • Immediately after depolarization both the activation and inactivation gates are open, allowing Na to enter the cell
  • A few milliseconds after, the activation gate is still open but the inactivation gates has closed and the channel is closed again (Na can’t enter the cell)
49
Q

State of Voltage-Gated Na+ and K+ Channels at RMP (-70 mV)

A
  • Na+: Activation Gate closed, Inactivation Gate open; Na+ unable to enter the cell
  • K+: Closed
50
Q

State of Voltage-Gated Na+ and K+ Channels once Threshold Potential is reached and AP starts (-70 to +35 mV)

A
  • Na+: Activation Gate rapidly opens, Inactivation Gate open (but very slowly starting to close); both gates open for brief period so Na+ can enter the cell
  • K+: Closed
51
Q

State of Voltage-Gated Na+ and K+ Channels when at Peak, 1-2 ms after AP (+35 mv to -70 mV)

A
  • Na+: Activation Gate open, Inactivation Gate closed; Na+ unable to enter cell
  • K+: Voltage-gated channel opens and K+ leaks out of the cell
52
Q

Sodium Channel Inactivation

A
  • the delayed decline in Na+ permeability upon depolarization
  • occurs as membrane potential decreases from +35 mV to -70 mV
53
Q

What side of the Voltage-Gated Na+ Channel is the activation gate located on?

A

Extracelluar Side (side that opens to the ECF)

54
Q

What side of the Voltage-Gated Na+ Channel is the inactivation gate located on?

A

Intracellular Side (side that opens to the ICF of the neuron)

55
Q

Effect of Depolarization on Voltage-Gated K+ Channels

A
  • Activation Gate opens upon depolarization, however it responds slowly to depolarization (slow activation)
  • K permeability increases with a delay following depolarization
  • K current is outward
  • These channels follow negative feedback loop during depolarization (depolarization by Na influx -> opening of voltage-gated K channels -> increased K permeability -> increase flow of K out of the cell -> repolarization of membrane potential (stops more voltage-gated K channels from opening)
56
Q

Absolute Refractory Period

A
  • Occurs when the inactivation gates of Voltage-Gated Na+ channels are closed
  • During this period no amount of depolarization can cause the cell to fire an AP
57
Q

Relative Refractory Period

A
  • Mainly overlaps with the hyperpolarization phase (undershoot, about -95 mv) during which conductance to K+ is higher than the normal level
  • During this period an AP can be evoked but only if a greater than usual depolarizing current is applied
58
Q

Accommodation

A
  • Process that occurs when the nerve or muscle cell is held at a depolarized level in a sustained manner
  • Occurs because depolarization closes inactivation gates of Na+ channels; if depolarization occurs slowly enough, Na+ channels close and remain closed
  • Upstroke of AP is affected because insufficient Na+ channels are open
  • Depolarization slowly activates K+ channels which increases K+ conductance
59
Q

Hyperkalemia

A
  • Occurs when the serum/blood K+ concentration increases
  • K+ equilibrium potential and RMP become less negative (depolarized) which can lead to muscle spasms which is followed by prolonged weakness
  • Accommodation can occur in patients with this condition
60
Q

Prolonged Weakness in Hyperkalemia

A
  • Activation gates on Na+ channels open in response to depolarization, while the inactivation gate on Na+ channels slowly begins to close
  • In response to prolonged depolarization (as in hyperkalemia), the inactivation gates close and remained closed; when the inactivation gates are closed Na+ channels are closed, regardless of the position of the activation gates
  • For an AP to occur both sets of gates on the Na+ channels must be open; if the inactivation gates are closed, no AP can occur
61
Q

Impact of Hypokalemia on Muscle

A
  • Occurs when there is decreased serum/blood K+ concentration
  • Reduced ECF K+ concentration hyperpolarizes the cell membrane (making the RMP more electronegative), which impairs the ability of the muscle to depolarize and contract, leading to muscle weakness
62
Q

Hypokalemic Periodic Paralysis

A
  • Rare neuromuscular disorder
  • Classified as hypokalemic when episodes occur in association with low K+ blood/serum levels
  • Attacks occur suddenly with generalized weakness; may be triggered by rest after vigorous exercise, stress, or high carb meal, often after a delay of several hours
  • Events that lead to attacks are often associated with an increased release of epinephrine (exercise, stress) or insulin (high carb meal), both of which cause movement of K+ into cells and low K+ blood levels
63
Q

Lidocaine

A
  • Blocks voltage-gated Na+ channels so that the inward current of the upstroke of the AP does not occur
  • Propagation of the AP, which depends on this depolarizing inward current, is also prevented

MSK Exam 2 (14 decks)

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