Block III: Action potential Flashcards

1
Q

What are NA/K ATPases?

A

maintains different ion concentrations inside versus outside the cell and pushes 3 Na+ ions out of the cell and 2 K+ ions into the cell; therefore using ATP

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2
Q

How is the charge inside of the membrane at resting potential because of Na+/K+ ATPases?

A

more negative inside

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3
Q

What is the normal concentration of Na+ outside the cell and inside?

A

Na+ outside high (≈ 150 mM), Na+ inside low (≈ 15 mM)

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4
Q

What is the normal concentration of K+ outside the cell and inside?

A

K+ outside low (≈ 5 mM), K+ inside high (≈ 100 mM)

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5
Q

What is the normal concentration of Cl- outside the cell and inside?

A

Cl- outside high (≈ 150 mM), Cl- inside low (≈ 10 mM)

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6
Q

What is the chemical gradient?

A

Different concentrations of ions in and out of cell

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7
Q

What produces electrical gradient?

A

produced by channels which are able to produce selective permeability to certain ions – diffusion down concentration gradient

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8
Q

What is the equilibrium potential?

A

When electrical gradient balances the chemical gradient

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9
Q

What is the value of the chemical gradient at its equilibrium potential?

A

equal and opposite to electrical force

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10
Q

What does Nerst equation calculate?

A

Calculates equilibrium potential for a given ion

E is equilibrium potential in volts
R is molar gas constant 0.082 J.K-1.mol-1
T is temperature in Kelvins
Z is valence, the number of charges per ion. Ca2+ has valence of 2, Cl- has valence of -1
F is Faraday’s constant = 96,487 C.mol-1
Ci, Co are outer and inner concentrations of the ion in mM

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11
Q

What is equilibrium potential and how do you calculate it?

A

Each ion has own equilibrium potential which can be calculated if you know the concentrations inside and outside the cell.
At its equilibrium potential, the chemical gradient is equal and opposite to electrical force. Thus, you have the same # of ions going in and out.

Nerst equation

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12
Q

Explain the meaning of each Nerst equation constant

A

E is equilibrium potential in volts
R is molar gas constant 0.082 J.K-1.mol-1
T is temperature in Kelvins
Z is valence, the number of charges per ion. Ca2+ has valence of 2, Cl- has valence of -1
F is Faraday’s constant = 96,487 C.mol-1
Ci, Co are outer and inner concentrations of the ion in mM

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13
Q

Whats the Na+ equilibrium potential ?

A

61mV

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14
Q

Whats the K+ equilibrium potential ?

A

-79mV

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15
Q

Whats the Cl- equilibrium potential ?

A

-71mV or -72mV

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16
Q

What calculates resting membrane potential?

A

Goldman(-Hodgkin-Katz) equation calculates resting potential

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17
Q

What is the normal or average value of resting membrane potential?

A

-50 to -70 and -60 to -65 is s common given example

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18
Q

What is the relative permeability?

A

number of ion channels in membrane that can pass that ion

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19
Q

What is the Na+ permeability at rest?

A

low

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20
Q

What is the K+ permeability at rest?

A

normally high, and its the most important component of resting potential

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21
Q

What is resting membrane potential?

A

Electrical potential (voltage) difference between inside of cell and outside. Usually ranges from -40 mV to -95 mV.

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22
Q

What is depolarization?

A

Cell membrane is made less negative (or more positive) on the inside. Membrane potential moves towards zero. (example give -40)

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23
Q

What is hyperpolarization?

A

Cell membrane is made more negative on the inside.
Membrane potential moves away from zero (downwards)

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24
Q

What are ion channels and what are they composed of?

A

Passageways or pores for ions to move through membrane with
Complex proteins inserted in lipid plasma membrane

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25
Q

What does ion-selective filters mean?

A

only certain ions can pass

26
Q

What does the total current through the channels depends on?

A

Total current through channels depends on channel conductance, number of channels, and the driving force on the ions

27
Q

What is the driving force of the ions?

A

Driving force for an ion = Em - Eion

the difference between resting potential and the ion’s equilibrium potential

28
Q

What is the driving force of Na+ in resting potential of -70 and equilibrium potential of 60?

A

For resting potential of -70 mV and ENa of 60, Na+ driving force = -70 - 60 = -130 mV (negative means inward)

29
Q

What is the driving force of K+ in resting potential of -70 and equilibrium potential of -80?

A

For resting potential of -70 mV and EK of -80, K+ driving force = -70 - -80 = +10 mV (positive means outward)

30
Q

WHta are the types of gated ion channels?

A

Voltage-gated (Voltage-dependent)
Chemical- or Ligand-gated

31
Q

What are voltage dependent channels?

A

pass ions at high rate when open.
Randomly open and close.
Probability of opening is greatly increased by membrane depolarization, decreased by hyperpolarization

32
Q

how do you study voltage dependent channels?

A

with patch clamp

33
Q

What is the secondary structure of alpha K+ channel genes

A

6 membrane-spanning alpha helices (S1 – S6)
Channel pore lined by pore loop (P) region and S6 (important for resting potential)
S4 region is voltage sensor
Positively charged amino acids move with depolarization

34
Q

How many subunits make the K+ channel

A

4 subunits with pore size making it selective for K+ (20x more K+ than Na+)

35
Q

Why are Voltage-dependent K+ channels imporant for?

A

Important role in development of resting potential (some are open at resting potential) Permability is relatively high here

Important for repolarization after action potential, in hyperpolarization and in neuronal inhibition

36
Q

Where can we find K+ channels?

A

nerves, muscle and glial cells

37
Q

What is Tetraethylammonium (TEA)?

A

Classic blocker of K+ channels making action potential stay up, (the overshoots gets long)

38
Q

Describe the Na+ voltage dependent channel

A

4 domains, each with
6 membrane-spanning alpha helices (S1 – S6)
Channel pore lined by pore loop (P) region and S6
S4 region is voltage sensor
Inactivation particle blocks pore (between unit III and IV)

Mainly selective for Na+ ions
(15x more Na+ than K+)

39
Q

Describe th eimportante of Na+ channels

A

Na+ channels have increased open probability when briefly depolarized.
Na+ channels open 10x faster than K+ channels
Important for rising phase of action potential
Maintained depolarization causes inactivation (open channel blocked by inactivation particle.
Recovery from inactivation requires repolarization for a few ms.

Na+ channels blocked by local anesthetics (eg. Lidocaine, Procaine) and by animal toxins (Tetrodotoxin) [BLOCKS ACTION POTENTIALS]

40
Q

What happens to P at threshold?

A

permeability increases for sodium and membrane depolarizes

41
Q

what happens in the overshoot of the action potential?

A

inactivation particle swung close, potassium channels open; driving force for potassium is high because they want to take the membrane voltage to more negative

42
Q

Explain the parts of the action potential

A

Rising phase, sodium, overshoot, falling phase, potassium, hyperpolarization

43
Q

What is the overshoot phase?

A

membrane voltage goes higher than 0

44
Q

potassium channels open in response to?

A

depolarization; (these channels are voltage dependent) dont open as fast as sodium channels

45
Q

What is a refractory period?

A

When you try to produce action potentials too close together, you would not be able to get another action potential; how long it takes for the particle to swing back open bc sodium channels are blocked you cannot get another action potential

46
Q

What is relative refractory period?

A

You can get a second action potential if you wait a little a give a stronger pulse (more current)

47
Q

Whta is absolute refractory period?

A

Particle is closed, so there no way you can get another action potential; a second AP cannot be produced

48
Q

Why does in after hyperpolarization, the voltage goes above 0 for a little while?

A

potassium channels are closing

49
Q

How is the Na+ current at the threshold?

A

At threshold, Na+ current in is just greater than K+ current out; Usually approx. 10 - 15 mV depolarization above resting potential;

50
Q

How is the Na+ current above threshold?

A

Above threshold, fast increase in Na+ current (more depolarization -> more channels open)

51
Q

What is the onset of K+ current?

A

K+ current has slower onset, repolarizes membrane and produces after-hyperpolarization

52
Q

Inactivation of which channels terminate an AP?

A

Na+ channels

53
Q

When do Na+ channels inactivation stop/recover?

A

during after hyperpolarization (de-inactivation)

54
Q

WHat affects the speed of an action potential?

A

Passive membrane properties (resistance, capacitance)

55
Q

large axons will have slower or faster APs?

A

faster

56
Q

How do propagation of AP happens?

A

Depolarization spreads electrotonically to neighboring membrane via local currents, depolarizing it to threshold.

57
Q

describe unmyelinated axons

A

Voltage-sensitive channels along axon
Slow conduction velocity
(approx. 5 m/s for 10 μm diameter, 10 m/s for 20 μm)
AP propagates by local currents

58
Q

describe myelinated axons

A

Myelin formed by Schwann cell or oligodendrocyte
Myelin increases membrane resistance – prevents current leakage
Na+ channels concentrated in Node of Ranvier
AP propagates by saltatory conduction
Faster conduction velocity
(approx. 60 m/s for 10 μm diameter, 120 m/s for 20 μm)

59
Q

Whats saltatory conduction?

A

Passive fast electrotonic spread of depolarizing currents to Node of Ranvier – many Na+ channels – generation of AP

Na+ channel inactivation prevents reverse propagation of AP
(“antidromic conduction”, normal conduction is “orthodromic”)

60
Q

explain MS (demyelination)

A

Autoimmune disease in which antibodies are directed against proteins in the myelin sheath of CNS neurons (oligodendrocytes).
Results in demyelination of CNS neurons.
Compromised myelin reduces membrane resistance and length constant – decreased conduction velocity
Reduced electrotonic conduction of depolarizing currents to next Node of Ranvier – Na+ channels do not reach threshold – transmission failure.
Eventually results in nerve degeneration.
Numbness, tingling, visual disturbances are initially reported.
Motor symptoms include weakness, tremor, lack of coordination.
MRI shows scarring in the CNS.

61
Q

explain Guillain-Barre

A

Destruction of Schwann cell myelin.
Results in demyelination of peripheral nerves.
Compromised myelin reduces membrane resistance and length constant – decreased conduction velocity
Reduced electrotonic conduction of depolarizing currents to next Node of Ranvier – Na+ channels do not reach threshold – transmission failure.
May progress rapidly
Progressive motor and sensory loss.
Eliminates reflexes.
Thought to be an immunologic reaction.
Most patients recover with gamma globulin administration or plasma exchange.

62
Q

explain Prion diseases

A

Prion
Infectious agent consisting mainly of protein that causes misfolding in endogenous prion membrane proteins.
Results in pathological protein aggregates (amyloids).

Creutzfeldt-Jakob Disease
Subacute spongiform encephalopathy.
Widespread neuronal loss and gliosis.
Motor (myoclonic jerks), visual and cerebellar abnormalities.
Dementia.
No effective treatment.
Patients usually die within year of onset.

Bovine Spongiform Encephalopathy (mad cow disease)
Spongy degeneration of brain and spinal cord in cattle.
May be transmitted to humans who eat infected tissues.