Action Potentials and AP Propagation in Nerves and Cardiac Cells Flashcards
Action potentials are
fundamental mechanism for electrical signaling within neurons and muscle cells and between nerves and muscle
what happens once AP generated
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
why are APs regenerative
bc they are all or nothing events that reproduce themselves at diff pets of cell or along axon
what determines direction of AP propagation
- location of initating stimulus
- number of Na+ channels available to be activated in direction current flowing
action potential is what direction in axons of nerve
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
cardiac muscle action potential
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)
myelination of axons in Schwann cells
optimizes cytoplasmic current flow and increases speed and safety factor for conduction
action potentials of different cell types
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
SA node cells
Sino-atrial node cells are pacemaker for cardiac cycle
depolarizing phase of action potential of SA node cells
due to opening of L-type voltage-gated calcium channels
SA node cells voltage-gated Na+ channels
do not express voltage gated Na+ channels
SA node action potentials
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
SA node input
SA node generates action potentials w/o external stimuli; SA nodes reach AP threshold via mechanism intrinsic to SA cells
Why are SA node cells pacemaker cells
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
HCN channles
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
cAMP
cyclic nucleotide produced from ATP by adenylate cyclase
SA node cells resting membrane potential
- don’t truly have one bc int contain voltage insensitive K+ channels
HCN channel inactivation
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
SA activation
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
T type channels
transient bc activate and inactivate like voltage gated Na+ channels in other excitable cells
control of pacemaker rate
controlled by ANS symp input (norepinephrine and epinephrine) -> increase pacemaker rate parasympathetic input (acetylcholine via muscarinic receptors) -> slows action potential
Sympathetic input pacemaker
- 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
parasympathetic input pacemaker
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
action potentials in ventricular myocytes are long because
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
ventricular myocyte action potential depolarization turns off cardiac inward rectifier currents
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
repolarization cardiac myocyte
- 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
for action potential to participate in signaling
action potentials generated at point A capable of changing membrane potential nearby and generating new action potential in previously unexcited patch membrane downstream
propagation of action potential from one compartment to another requires
- A driving force for current flow
2. A connection between two compartment
Driving force
difference in membrane potential (transmembrane voltage) btwn compartment that generated AP and compartment that hasn’t yet generated AP
current flow between excited and adjacent resting patch of membrane
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
propagation of action potential at ummyelinated axon
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
To initiate an AP
-stimulus must activate many Na+ channels so pos feedback from small depolarization gained from addition newly activated channels
AP threshold
- 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
Action potential vs spread of current
- 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
action potential propagation inclues
both ionic currents through open channels and passive currents associated with charging and discharging membrane capacitor
capacitative current
change in charge on phospholipids
Na+ and K+ action potential
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
contributions to refractoriness of axon upstream of AP
- gK+ remains high are action potential and Na+ channels are inactivated -> refractoriness axon upstream of AP
propagation of action potential
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
myelinated nerve fibers
- 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
speed action potential propagation determined by
- resistance cytoplams
- resistance of pathway across membrane
myelin and transmembrane current
- 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
action potential propagation in myelinated nerves called
saltatory conduction (means to jump)
action poteital propigation in myelinated nerves
- 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
demyelination nerve fibers
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)
demyelination worse than not being myelinated at all
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
explain slow conduction bc demyelination
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
propagation cardiac action potentials
- 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
gap junctions between cardiac cells
comprised of connexons which are couplings of 6 connexins that terminate regions of cell membrane in cardiac cells
propagation action potential in cardiac cells
occurs bc depolarizing current generated by excited patch membrane in one myocyte transferred via connexon to unexcited patch membrane in adjacent myocyte
myocytes in cardiac cells separated by
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
propagation of action potential between cardiac cells occurs bc
depolarizing current generated by excited patch membrane in one myocyte transferred via connexon to unexcited patch of membrane in adjacent myocyte
resistance between adjacent cells in normal heart
very low because gap junctions between myocytes nearly all open
nerve and muscle cell different action potentails
different shapes and speeds result of different ion channels expressed by diff types excitable cells
what plays most critical role in propagating action potential in nerves
voltage-dependent activation and inactivation of Na+ channels
addition of depolarizing current to interior oc cell
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
Na+ influx via open Na+ channels
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
flow of action potential along axon
hillock -> terminal
axon terminal voltage gated ion channels
no voltage gated Na+ channels yes voltage gated Ca2+ channels, let Ca2+ in allow vesicle fusion and leading to neurotransmitter release
what propagates action potential
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
large vs small diameter axons
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
if you bang eblow
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.
refractory region
in temporary condition reverts back to available when membrane repolarizes
membrane capacitance discharge
allows current flow to be fast
Nodes of ranvier
have K+ channels caspr Na+ channels caspr K+ channels
stages SA node AP
if -> ica(t) -> ica(l) -> ik -> if
cardiac myocyte stages AP
ik -> ina -> ikto -> Ica(l) ->ik
what are necissary for pacemaker function
HCN channel properties required for pacemaker function
HCN channels and Na+
HCN channels let Na+ through BUT are not Na+ gated channels (which are fast voltage gated)
SA node pacemaker potentials
- 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
ikto
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
when do voltage gated Ca2+ shut in cardiac myocyte AP
when K+ shuts them down
action potential through heart
SA node action potential rapidly conducted through atrium to AV node through His-purkinje network to ventricular myocardium
pore structure of gap junction channel
a lot of negatively charged Has lining core allows for cations to flow through
excitable cells have large
resting membrane potential that facilitates recovery voltage gated Na+ and Ca2+ from inactivated states
what excitable cells do not have all or none action potentials in response ot extrinsic stimuli
pacemaker cells
pacemaker cells do not have
RMP
what provides intrinsic depolarizing effect in pacemaker cells
HCN channels
changes in serum chemistry can lead ot
changes in electrical activity; low Ca2+ levels usually bc kidney issue
purpose of neuron
gather incoming signals, integrate them and transmit info to connected cells w/ in network by propagating action potential
action potentials conduction between cardiac cells through
gap junctions
