Action Potentials and AP Propagation in Nerves and Cardiac Cells

Question 1

Action potentials are

Answer 1

fundamental mechanism for electrical signaling within neurons and muscle cells and between nerves and muscle

Question 2

what happens once AP generated

Answer 2

generated at point A propagated to point B; propagate by combo of passive spread form pt A through low resistance of cytoplasm ot pt B where new AP is generated

Question 3

why are APs regenerative

Answer 3

bc they are all or nothing events that reproduce themselves at diff pets of cell or along axon

Question 4

what determines direction of AP propagation

Answer 4

• location of initating stimulus

- number of Na+ channels available to be activated in direction current flowing

Question 5

action potential is what direction in axons of nerve

Answer 5

unidirectional in axons of nerve from pt of initiation in axon hillock -> presynaptic terminal bc inactivation Na+ channels at initiation point means although current spreads all direction next action potential generated must be in unexcited axon closer to nerve terminal

Question 6

cardiac muscle action potential

Answer 6

action potential propagated from excited cell to unexcited cell via gap junctions that connect them (wnt go to previously excited cell bc it is refractory)

Question 7

myelination of axons in Schwann cells

Answer 7

optimizes cytoplasmic current flow and increases speed and safety factor for conduction

Question 8

action potentials of different cell types

Answer 8

are different in shape and duration bc cells contain different variants of voltage-sensitive ion channels that participate in generating their action potentials
- cardiac myocytle action potential MUCH longer (500x) than action potential of neuron; neuronal signaling is v fast

Question 9

SA node cells

Answer 9

Sino-atrial node cells are pacemaker for cardiac cycle

Question 10

depolarizing phase of action potential of SA node cells

Answer 10

due to opening of L-type voltage-gated calcium channels

Question 11

SA node cells voltage-gated Na+ channels

Answer 11

do not express voltage gated Na+ channels

Question 12

SA node action potentials

Answer 12

initiated by opening of 3 types voltage-gated channels and repolarization is due to activation of single type voltage-gated K+ channel in delayed rectifier group

Question 13

SA node input

Answer 13

SA node generates action potentials w/o external stimuli; SA nodes reach AP threshold via mechanism intrinsic to SA cells

Question 14

Why are SA node cells pacemaker cells

Answer 14

bc SA node cells have set of channels that produces funny current If
- these channels = hyperpolarization and cyclic-AMP activated cation channels aka HCN channels

Question 15

HCN channles

Answer 15

aka hyper polarization and cyclic-AMP activated cation channels
characteristics:
1. Activated by hyperpolarization and inactivated by depolarization
2. Activation is modulated by increasing or decreasing intracellular cAMP concentration
3. Permeable to Na+ and K+ but more permeable to Na+ ions so equilibrium potential is about -30mV

Question 16

cAMP

Answer 16

cyclic nucleotide produced from ATP by adenylate cyclase

Question 17

SA node cells resting membrane potential

Answer 17

• don’t truly have one bc int contain voltage insensitive K+ channels

Question 18

HCN channel inactivation

Answer 18

inactivate well before peak of AP depolarization; do not interfere with repolarization occurring after delayed rectifier channels activated; HCN channels reopen during down stroke of AP bc open probability continues to increase during repolarization phase culminating in gradual depolarization (pacemaker potential) which brings cell membrane closer to AP threshold

Question 19

SA activation

Answer 19

HCN channels open and depolarize SA node cells, fit opening voltage-gated transient (T-type) Ca2+ channels activate these two things together -> depolarization SA node cells enough to activate L-type Ca2+ channels which responsible for upstroke SA node action potential -> cell depolarizes to >-20mV voltage-gated delay rectifier type K+ channels open and action potential begins to depolarize

Question 20

T type channels

Answer 20

transient bc activate and inactivate like voltage gated Na+ channels in other excitable cells

Question 21

control of pacemaker rate

Answer 21

controlled by ANS
symp input (norepinephrine and epinephrine) -> increase pacemaker rate
parasympathetic input (acetylcholine via muscarinic receptors) -> slows action potential

Question 22

Sympathetic input pacemaker

Answer 22

• B adrenergic effects symp stimulation -> increase in intracellular cAMP -> activation HCN channels and increase slope pacemaker potential
• increase cAMP -> increase L-type Ca2+ channel phosphorylation potentiates increases open time of channels and permits increase in calcium influx

Question 23

parasympathetic input pacemaker

Answer 23

slows heart rate
- produced by acetylcholine release from vagus nerve and subsequent activation of cardiac muscarinic receptors; intracellular effect is decrease production cAMP -> prolonged hyperpolarization and decrease of slop of pacemaker potential

Question 24

action potentials in ventricular myocytes are long because

Answer 24

upstroke of ventricular mycocyte AP mediated by opening fast-activating Na+ channels and depolarization is sustained by activation of L-type Ca2+ channels which are main component responsible for long plateau

• voltage and time dependent activation L-type Ca2+ channels is highly regulated by synaptic and hormonal stimulation
• ventricular myocyte action potential depolarization turns off cardiac inward rectifier currents

Question 25

ventricular myocyte action potential depolarization turns off cardiac inward rectifier currents

Answer 25

occurs because large intracellular cations - channel blockade -> depolarization maintained and Ca2+ entry through L-type channels sustained allowing intracellular Ca2+ concentration to rise sufficiently to activate ryanodine receptors to stimulate cardiac muscle contraction if these channels were blocked K+ efflux would oppose activation Na+ and Ca2+ channels and cell would depolarize too rapidly and cardiac muscle would not contract

Question 26

repolarization cardiac myocyte

Answer 26

- cardiac version delayed rectifier K+ channels (Ikv1.5) activate slowly compared to Ikv1 types in neurons - this allows appreciable K+ efflux doesnt begin till after Ca2+ dependent plateau developes, longer plateau means more time for Ca2+ to enter to ensure muscle contraction - slow Ikv1.5 return membrane toward resting potential inward rectifier K+ channels responsible for resting potential in cardiac myocytes become unblocked bc forces driving Mg2+ and polyamides from cytoplasm into channels are reduced -> hand over of repolarization mechanisms from Ik1.5 to Ik1r channels

Question 27

for action potential to participate in signaling

Answer 27

action potentials generated at point A capable of changing membrane potential nearby and generating new action potential in previously unexcited patch membrane downstream

Question 28

propagation of action potential from one compartment to another requires

Answer 28

1. A driving force for current flow | 2. A connection between two compartment

Question 29

Driving force

Answer 29

difference in membrane potential (transmembrane voltage) btwn compartment that generated AP and compartment that hasn't yet generated AP

Question 30

current flow between excited and adjacent resting patch of membrane

Answer 30

passive; if passive current spread from upstream depolarization is sufficient to activate more than a few voltage-gated ion channels in downstream patch excitable membrane than AP generated

Question 31

propagation of action potential at ummyelinated axon

Answer 31

T1 point A: depolarizing stimulus -> activation voltage gated Na+ channels -> Na+ flows into axon -> depolarizes membrane -> activates more Na+ channels -> threshold reached -> action potential -> T2 point B: curent flows through cytoplasm to point B-> new action potential generated T2 point A: voltage-gated K+ channels open slowly starting at T1 open at T2 -> K+ efflux -> repolarizing membrane This process continues down axon action potential to next point repolarization at previous pt where just had last AP

Question 32

To initiate an AP

Answer 32

-stimulus must activate many Na+ channels so pos feedback from small depolarization gained from addition newly activated channels

Question 33

AP threshold

Answer 33

- membrane potential where majority of available Na+ channels open and membrane potential rises rapidly during upstroke of AP - "membrane potential where no additional external stimulation needed for AP to fire (ie intimate and continue the upstroke) - Threshold carries based on type of cell, diff ionic conditions, - ability of patch of nerve to generate an AP dependent on density of voltage gated Na+ channels in unexcited patch that are available

Question 34

Action potential vs spread of current

Answer 34

- action potential propagation is unidirectional along axon while passive spread of current in axoplasm is in both directions; this is bc Na+ channel inactivation keeps action potential propagation unidirectional

Question 35

action potential propagation inclues

Answer 35

both ionic currents through open channels and passive currents associated with charging and discharging membrane capacitor

Question 36

capacitative current

Answer 36

change in charge on phospholipids

Question 37

Na+ and K+ action potential

Answer 37

K+ and Na+ channels open Na+ flows into K+ flows out of axon/ cell Na+ channels then in refractory period and temporarily inactivated and K+ efflux through open channels depolarizes membrane

Question 38

contributions to refractoriness of axon upstream of AP

Answer 38

- gK+ remains high are action potential and Na+ channels are inactivated -> refractoriness axon upstream of AP

Question 39

propagation of action potential

Answer 39

Na+ entry through open Na+ channel -> difference in membrane potential between open depolarized channel and adjacent membrane at resting potential -> positive charge from L to R building in cell -> positive charge on extracellular side of membrane moving away from cell membrane back toward L side patch where extracellular potential more negative -> continued movement pos charge in cytoplasm L to R depolarizes membrane potential past threshold Na+ channel opens -> Na+ enters cell -> new action potential -> depolarize next patch membrane to R

Question 40

myelinated nerve fibers

Answer 40

- In CNS oligodendrocyte glial cells ensheath axons - in PNS myelination by Schwann cells wrapped around axons - propagation action potential same as in unmyelinated Neve fiber but excitable membrane patches containing voltage-gated Na+ channels located at nodes Ranvier while membrane sheathed in myelin inexcitable

Question 41

speed action potential propagation determined by

Answer 41

- resistance cytoplams | - resistance of pathway across membrane

Question 42

myelin and transmembrane current

Answer 42

- multiple layers of myelin create high resistance barrier between cytoplasm and extracellular space preventing transmembrane current leaking across cell membrane - bc v little current leaking action potentials propagate faster in myelinated axons than unmyelinated axons

Question 43

action potential propagation in myelinated nerves called

Answer 43

saltatory conduction (means to jump)

Question 44

action poteital propigation in myelinated nerves

Answer 44

- same steps as in unmmyelinated but voltage gated Na+ channels at nodes ranvier rest of membrane inexcitable - axon membrane capacitance reduced and axon membrane resistance increased in myelinated axon which allows for more efficient flow current to next node through low resistance of cytoplasm

Question 45

demyelination nerve fibers

Answer 45

autoimmune dx and other demyelinating disorders myelin sheath damged by inflammation and may be lost permanetely - acutely demyelinated axon segments btwn nodes Ranvier int express Na+ channels and depolarization at one node must be lrg enough to reach next node w/o insulation - acute demyelination (loss myelin patchy) -> action potential conducted more slowly - loss myelin involving more than few nodes can -> compete failure of propagation - as more myelin lost -> loss protein secreted by Schwann cells (caspr) and Na+ and Kvr channels become more evenly distributed along length axon allowing some restoration of conduction (this recovery will take time and will only be partial)

Question 46

demyelination worse than not being myelinated at all

Answer 46

bc cell membranes of unmyelinated nerve fibers lack high resistance insulation which makes them more prone to leakage but excitable membrane patches in these cells contiguous with one another and leak of current between two patches of excitable membrane = v compensated for by leg influx depolarizing current provided and voltage gated Na+ and K+ channels which are uniformly distributed and close enough together to allow for effective action potential propagation

Question 47

explain slow conduction bc demyelination

Answer 47

depolarizing current generated by Na+ influx in L node escapes across demyelinated segment of fiber rather than flowing through axoplasm so membrane R node less depolarized and it takes longer for sufficient depolarization to accumulate in R node and for it to reach threshold and fire

Question 48

propagation cardiac action potentials

Answer 48

- propagation action potentials between cardiac myocytes necessary to synchronize cardiac contraction - rapid AP propagation heart possible bc low resistance pathways formed by open gap jnxions electrically coupling cardiac cells to each other longitudinally and transversely -> synchronized network referred to as syncytium

Question 49

gap junctions between cardiac cells

Answer 49

comprised of connexons which are couplings of 6 connexins that terminate regions of cell membrane in cardiac cells

Question 50

propagation action potential in cardiac cells

Answer 50

occurs bc depolarizing current generated by excited patch membrane in one myocyte transferred via connexon to unexcited patch membrane in adjacent myocyte

Question 51

myocytes in cardiac cells separated by

Answer 51

``` gap junctions (electrically) (actual membrane patches are contiguous within given cardiac muscle cell) - gap junctions provide conduit for current flow from excited to unexcited myocyte ```

Question 52

propagation of action potential between cardiac cells occurs bc

Answer 52

depolarizing current generated by excited patch membrane in one myocyte transferred via connexon to unexcited patch of membrane in adjacent myocyte

Question 53

resistance between adjacent cells in normal heart

Answer 53

very low because gap junctions between myocytes nearly all open

Question 54

nerve and muscle cell different action potentails

Answer 54

different shapes and speeds result of different ion channels expressed by diff types excitable cells

Question 55

what plays most critical role in propagating action potential in nerves

Answer 55

voltage-dependent activation and inactivation of Na+ channels

Question 56

addition of depolarizing current to interior oc cell

Answer 56

stimulates opening of voltage-gated Na+ channels causing capacitance across membrane patch to discharge -> rapid change charge depolarizing membrane above threshold potential for opening nearby fast sodium channels

Question 57

Na+ influx via open Na+ channels

Answer 57

creates voltage gradient between excited region membrane and neighboring unexcited regions; flow depolarizing current from excited to unexcited region raises unexcited to threshold potential and opens Na+ channels

Question 58

flow of action potential along axon

Answer 58

hillock -> terminal

Question 59

axon terminal voltage gated ion channels

Answer 59

no voltage gated Na+ channels yes voltage gated Ca2+ channels, let Ca2+ in allow vesicle fusion and leading to neurotransmitter release

Question 60

what propagates action potential

Answer 60

phospholipid bilayer cell has neg charge and when Na+ ions cross -> change membrane charge when crossing bc change voltage in cell -> change charge membrane and the disrarche of charges of membrane propigates action potential

Question 61

large vs small diameter axons

Answer 61

large diameter axons conduct faster than small bc resistance to current flow through cytoplasm decreases as cross sectional area axon increases - small usually carry pain and temp - large usually carry light tough

Question 62

if you bang eblow

Answer 62

starting in middle long axon so action potential can go both ways at first bc pt toward hand hands been activated leads to stinging down arm ect.

Question 63

refractory region

Answer 63

in temporary condition reverts back to available when membrane repolarizes

Question 64

membrane capacitance discharge

Answer 64

allows current flow to be fast

Question 65

Nodes of ranvier

Answer 65

have K+ channels caspr Na+ channels caspr K+ channels

Question 66

stages SA node AP

Answer 66

if -> ica(t) -> ica(l) -> ik -> if

Question 67

cardiac myocyte stages AP

Answer 67

ik -> ina -> ikto -> Ica(l) ->ik

Question 68

what are necissary for pacemaker function

Answer 68

HCN channel properties required for pacemaker function

Question 69

HCN channels and Na+

Answer 69

HCN channels let Na+ through BUT are not Na+ gated channels (which are fast voltage gated)

Question 70

SA node pacemaker potentials

Answer 70

1. HCN channels (If) open Na+ influx depolarizing membrane 2a. Transient Ca2+ (T-type) channels rapidly open and depolarize SA node above action potential thrshold 2b. HCN channels turn off when membrane depolarized 3a. Depolarization activates L-type Ca2+ channels generating upstroke action potential 3b. Transient Ca2+ (T type) channels turn off 4a. Voltage activated K+ channels open and depolarize membrane 4b. Repolarization situations activation HCN channels cycle repeats

Question 71

ikto

Answer 71

in cardiac mycocute AP; transiet k+ current brief and all it does is stop AP from being > amplified than it is an irregularity in this current -> change current

Question 72

when do voltage gated Ca2+ shut in cardiac myocyte AP

Answer 72

when K+ shuts them down

Question 73

action potential through heart

Answer 73

SA node action potential rapidly conducted through atrium to AV node through His-purkinje network to ventricular myocardium

Question 74

pore structure of gap junction channel

Answer 74

a lot of negatively charged Has lining core allows for cations to flow through

Question 75

excitable cells have large

Answer 75

resting membrane potential that facilitates recovery voltage gated Na+ and Ca2+ from inactivated states

Question 76

what excitable cells do not have all or none action potentials in response ot extrinsic stimuli

Answer 76

pacemaker cells

Question 77

pacemaker cells do not have

Answer 77

RMP

Question 78

what provides intrinsic depolarizing effect in pacemaker cells

Answer 78

HCN channels

Question 79

changes in serum chemistry can lead ot

Answer 79

changes in electrical activity; low Ca2+ levels usually bc kidney issue

Question 80

purpose of neuron

Answer 80

gather incoming signals, integrate them and transmit info to connected cells w/ in network by propagating action potential

Question 81

action potentials conduction between cardiac cells through

Answer 81

gap junctions