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Cellular Week 4 > Action Potentials/Excitiability > Flashcards

Action Potentials/Excitiability Flashcards

1
Q

HOW MANY K+ IONS NEED TO CROSS THE MEMBRANE TO GENERATE 0.1 VOLT?

A

Only 10-12 Moles of K+ ions per cm2 of membrane!

NOT the floodgates opening

NO change in the electroneutrality of the bulk ion concentrations in the ECF and ICF

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2
Q

When potassium channels are the only channels open at rest RMP = EK.

When the resting membrane is permeable to both K+ and Na+
the RMP is INTERMEDIATE between EK and ENa

A

….

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3
Q

During signaling, the membrane potential does not stay constant at RMP but changes briefly… changes = action potentials

A

…

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4
Q

Cells which use action potentials to control physiological functions are referred to as excitable cells. These include nerves and muscles (skeletal, cardiac and smooth), sensory transducing cells and endocrine cells, to name a few. Excitable cells can modulate their ability to fire action potentials, i.e. their excitability, to respond to changing conditions.

A

…

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5
Q

the reference point is always the ECF, 0 mV. The RMP is the potential of the inside of the membrane

A

…

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6
Q

critical threshold potential (about -60 mV for nerve and muscle)

A

…

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7
Q

In some cells the membrane repolarizes briefly to a value more negative or positive than the initial RMP, and this phase is termed the afterpotential. When the peak of the action potential exceeds 0 mV, it is called the overshoot

A

…

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8
Q

Most action potentials overshoot to a positive value, approaching ENa

A

….

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9
Q

Together, the inactivation of Na channels and the opening of K channels restores the PNa/ PK ratio to its initial low value (↓PNa/PK)

A

….

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10
Q

The RMP is restored to its initial value when the number of K+ ions which moved outward equals the equals the number of Na+ ions which moved inward.

A

…

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11
Q

The rapid, sequential changes in Na+ and K+ permeability are mediated by two key proteins …….?

A

the voltage dependent Na channel and the voltage-dependent K channel

The voltage-dependent K channel is a separate protein from the resting K channel

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12
Q

The resting K channel operates largely at negative potentials near the RMP, while the voltage dependent, delayed K channel is largely closed near the RMP and opens only during the action potential

A

…

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13
Q

The voltage dependent Na+ channel can assume 3 diff conformations….?

A

CLOSED (resting), OPEN (active) and INACTIVE.

Transitions between states are controlled by voltage and time — i.e. the conformation which the channel assumes depends on the amplitude and duration of the membrane potential

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14
Q

The Na channel opens briefly when the membrane potential depolarizes above its threshold potential of about ~ -60 mV. The channel then moves spontaneously to an inactive conformation, where further Na+ influx is blocked. The membrane potential must return to the RMP for tens of milliseconds to reset the Na channel to the closed state, from which it can reopen.

A

…

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15
Q

. Na channels can open only from the closed state (for this reason the closed state is also called the available state)

A

….

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16
Q

Fast inactivatoin?

A

transient depolarization ABOVE THRESHOLD depolarization

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17
Q

slow inactivation?

A

steady sub threshold depolarization, RMP to t.p.

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18
Q

what are the functional conformations of K+ voltage dependent channel?

(delayed rectifier)

A

resting

active

The transition from closed to open is slower than for Na channels and occurs at a more depolarized potentials. Its threshold potential is ~ -10 mV

Consequently, Na channels open first during the action potential, and K channels open a split second later

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19
Q

Which way do Na+ and K+ move?

A

The DIRECTION depends on the energy difference
between Em and the equilibrium potential for each ion

Difference = driving force!

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20
Q

The electrochemical driving force acting on a Na+ ion is the energy difference between the membrane potential and ENa, (Em - ENa). The driving force for Na+ entry is greatest at the threshold potential, where (Em - ENa) = -130 mV. Na+ ions move inward down their electrochemical gradient until a new equilibrium is established—that is, when Em approaches ENa. At ENa, there is no further Na+ movement (even though the pore is open), because the driving force has collapsed to 0 mV. Similarly, the driving force for K+ movement is (Em − EK); Figure I-19. At rest, there is little driving force acting on a K+ ion because
Em » EK. However, when voltage-dependent K channels open during the action potential, there is a large driving force for K+ efflux, because Em is far positive of EK. At the peak of the action potential, (Em - EK) = +120 mV. K+ ions move outward until equilibrium is re-established near EK.

A

…

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21
Q

By convention, a NEGATIVE driving force indicates inward movement of positive charges

A

….

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22
Q

A POSITIVE driving force drives outward current. K+ ions flow outward through open K channels, down their electrochemical gradient.

A

….

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23
Q

The driving force for K+ movement is maximum near the peak of the action potential, where (Em - EK) = +30 - (-90 ) = + 120 mV

A

….

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24
Q

During an AP, the driving force for inward Na+ movement is greatest at the

A

threshold potential

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25
Q

During an AP, the driving force for inward Na+ movement is LEAST at the

A

PEAK

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26
Q

Ion movements during the AP can be measured either as FLUXES or CURRENTS

A

….

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27
Q

Current is measured in…

A

amperes!
coulombs per sec per cm2

physiologists use this term!

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28
Q

flux is measured in…

A

moles of ion per sec per cm2

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29
Q

relationship between ion flux and current?

A

faraday’s constant!

10^5 coulobs/mole

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30
Q

The change in identity of the charges on the membrane surface is immeasurably small for a single action potential (only ~ 1 picoMole of ions per cm2 of membrane

A

…

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31
Q

Absolute refractory period (ARP)?

A

the interval during which a second action potential cannot be elicited for any amplitude stimulus. – sodium channels in the inactive state (not resting)

32
Q

relative refractory period (RRP)

A

the period following the absolute refractory period during which excitability is depressed but not blocked; during this period a subsequent action potential may be elicited depending on the stimulus amplitude and/or the number of Na channels that have returned from the closed state

33
Q

functional refractory period FRP

A

minimum interval between action potentials which can actually be achieved by a particular cell. It will occur somewhere in the RRP and is operationally defined by a measurement

34
Q

The refractory period helps prevent abnormal repetitive firing in skeletal muscles and prevents arrhythmias in cardiac muscle.

A

….

35
Q

A refractory period insures that an action potential moves in one direction along an axon (see propagation section below) or along the conducting pathways in the heart

A

…

36
Q

FRP is defined by a measurement. To measure the FRP, apply an, excitatory depolarization to a nerve, then re-apply the same stimulus after 1, 2, 5, 10 or more milliseconds. If the nerve fires a second AP only after 10 ms, then its FRP is 10 ms.

A

…

37
Q

Typically, nerves and skeletal muscles have a large safety factor and can fire a second action potential if only a few percent of Na channels have reset to the closed state

A

….

38
Q

At -70 mV, 50% of Na+ channels are inactive

still fire but the rate of rise and overshoot will be reduced a

A

…

39
Q

At -50 mV, 100 percent of sodium channels are inactive!

the membrane will not fire an AP even in response to a larger-than-normal stimulus

A

….

40
Q

HOW DOES A CELL MODULATE MEMBERANE EXCITABILITY to RESPOND to DIFFERENT CONDITIONS?

A

Changes the RMP!!

EXAMPLE: stress increases epinephrine (adrenaline) Epinephrine increases the permeability of resting K channels in nerve and muscle.
This drives the RMP more negative, moves Na channels to the closed/available conformation. These cells are more responsive when needed for “fight or flight”.

41
Q

How do cells change their RMP under different conditions?

A

Typically, by having resting K+ channels whose activity
is regulated by cellular metabolites, hormones or neurotransmitters.

This alters the Pna/Pk ratio, which in turn alters RMP

42
Q

Skeletal muscle cells have some of the most negative resting potentials in the body.

A

….

43
Q

neurons typically have more depolarized RMPs, near -70 mV. This is the mid-point of voltage-dependent inactivation by the slow pathway, where channels are distributed about 50:50 between closed and inactive states. Having the RMP near the mid-point of the slow inactivation process allows the nerve to modulate its resting potential up or down. (the set point for most regulated biological processes is near the mid-point of the operating range). By modulating the RMP, nerves can adapt their excitability to dynamically changing conditions.

A

…

44
Q

Some cells use Ca2+ channels to generate APs

ex. SA node and ventricular myocytes

Some cells use Ca2+ entry through voltage-dependent Ca channels to generate the initial depolarization or to prolong a depolarization initiated by Na+ influx

A

..

45
Q

SA node cells in the heart, pancreatic beta cells, and certain smooth muscle cells use only Ca channels to generate the depolarization phase of the action potential

A

…

46
Q

Ca-dependent action potentials have a slower depolarization phase and longer duration than the nerve action potential

slower opening and require greater depolarization

A

..

47
Q

Ca2+ flows inward

A

..

48
Q

ventricular myocytes use both Na and Ca channels. Na drives the initial rapid depolarization and then Ca opens to extend the depolarization… look at graph

A

..

49
Q

For calcium equilibrium, need to divide 61 by 2!!

A

…

50
Q

Some cells use Cl- channels to help depolarize the AP

Because Cl- is negatively charged, its movement into the cell down its electrochemical gradient aids repolarization.

A

..

51
Q

An action potential is triggered when a stimulus perturbs the normal RMP, depolarizing it to threshold. In nerve and skeletal muscle, the stimulus is an excitatory post-synaptic potential at the synapse ( EPSP) or an end plate potential (EPP) at the neuromuscular junction.

A

…

52
Q

How is an AP initiated on the cell membrane?

A

a local depolarization brings one area of membrane to TP

ex. post synaptic potentials
end plate potentials
pacemaker potentials

53
Q

Positive feedback between Na channel opening and the membrane potential produces an all-or-nothing depolarization- i.e. an action potential

This process is opposite to homeostasis, which uses negative feedback

A

…

54
Q

3 ways a depolarization can spread along a membrane from one site of stimulus… passive, active, saltatory

A

…

55
Q

passive? (electrotonic conduction)

A

no Na+ channels

The amplitude of the depolarization decreases exponentially with distance from the site of origin

FAST

56
Q

active

A

na+channels

FASTER

57
Q

saltatory

A

Na+ channels and myelin

FASTEST!

58
Q

In PASSIVE CONDUCTION,
AMPLITUDE of the depolarization DECREASES
with distance along the axon

A

…

59
Q

greater permeability means greater loss of charges along the bilayer, lower charge density, and greater voltage loss with distance. i.e. a shorter space constant

A

…

60
Q

what is the space constant?

A

The space constant is the distance from the stimulus at which the depolarization has decreased to 37% of the initial amplitude.

61
Q

What factors determine the space constant?

A

resting membrane permeability, the conductivity of the cytosol, and the axon diameter

62
Q

space constant is greater in larger diameter axons and is shorter with higher membraine permability

A

…

63
Q

the axon hillock contains a high density of Na+ channels and is the trigger zone for initiating an action potential

A

…

64
Q

In contrast to the EPSP amplitude which decreases along the cell body, the all-or-nothing action potential depolarizes the membrane to the same potential at every point along the axon

A

….

65
Q

Information coding at the soma of a neuron is ANALOG. Depolarizations coming from different synaptic inputs simply add and subtract to generate a net depolarization

A

…

66
Q

In contrast, information coding along the axon is DIGITAL. The AP reaches the same amplitude along the length of the axon; it is a YES/NO signal to downstream synapses

A

…

67
Q

Passive – spread out in both directions! - depolarizes regions adjacent

A

….

68
Q

saltatory conduction - passive and active combo (Na+ myelin)

A

..

69
Q

actie conduction is a nerve WITH na+channels

A

….

70
Q

Nodes have the highest density of Na+ channels known!

A

…

71
Q

saltatory – The depolarization moves by electrotonic conduction through the internodes, and by active propagation at the nodes

A

….

72
Q

What cells produce myelin?

A

glial cells!

73
Q

myelin greatly decreases the electrical capacitance of the internodal membrane. Fewer charges are required to depolarize the membrane to the same potential

A

…

74
Q

Electrotonic conduction is greatly facilitated by the myelin sheath, which speeds electrotonic currents, and by the absence of ion channels which increases the space constant of the internode membrane

A

…

75
Q

large myelinated is faster than small myelinated

A

…

76
Q

Increase nerve conduction velocity?

A

Increase nerve diameter
Increase density of Na channels – more depolarizing current
Increase myelin thickness

Cellular Week 4 (11 decks)

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