Cardiac Electrophysiology Flashcards
what is the difference between how biophysicists and electrocardiologists look at a muscle cell?
biophys-intracellular electrodes
electrocard-extracellular electrodes
what is the resting potential of a cardiac muscle cell?
-80 mV (negative inside)
what is an equilibrium potential? what equation is used in this case?
the voltage obtained for a given concentration gradient of a single ion at equilibrium across a semipermeable membrane
Nernst Equation
what is gibbs-donnan equilibrium? what is an example of this?
there is an impermiable polyelectrolite on one side of a membrane that is permeable to salts.
equilibrium across capillary membranes if there are charged proteins in the blood but not in the interstitial fluid
when does gibbs-donnan equilibrium result in unequal distribution of salts across a membrane? what sign does the resulting membrane potential have?
when the pH differs from the isoelectric point of the polyelectrolyte
the membrane potential has the same sign as the charge of the polyelectrolyte
what is a diffusion potential? what equation is used in this case?
when two or more ions have varying permeabilities to a membrane
goldman-hodgkin-katz equation
what is the theory of electrodiffusion?
it describes the independent passive movements of ions across membranes under the influence of concentration gradients and electrical forces
what are two examples of diffusion potentials?
resting potentials and action potentials
what are epithelial membrane potentials?
differences of electrical potential that occur between two solutions when the membrane is a layer of cells (kidney and GI system)
according to the nernst equation, what is the result of raising the concentration of extracellular K+? intracellular K+?
extracellular- makes Ek less negative and is depolarizing
intracellular- makes Ek more negative and is hyperpolarizing
at a low external K+, how does the membrane potential compare to what is predicted by the nernst equation? why is this true?
it is more positive
this happens because the membrane potential is influenced by both K+ and Na+
when is the influence of Na+ on membrane potential greatest?
at a low concentration of K+
what two conditions hyperpolarize the cell? why?
raising internal concentrations of K+ (increases outward K+ gradient)
raising internal concentrations of Na+ (decreases inward Na+ gradient)
what two conditions depolarize the cell? why?
raising external concentrations of K+ (decreases the outward K+ gradient)
raising external concentrations of Na+(increases the inward Na+ gradient)
why do different cell types have different membrane potentials if they have similar intracellular and extracellular concentrations of K?
cell membranes have varying relative permeabilities of Na+ to K+
greater relative permeability of Na+/K+, lower the resting potential
what is a positive and negative current?
positive: outflux of positive ions
negative: influx of positive ions
what does ohm’s law state? what is the slope of the current vs voltage plot?
current is directly proportional to voltage
the slope is the inverse of the resistance or conductance
what is rectification?
conductance differs for inward and outward currents
what is outward rectification and inward rectification? what does this do to the current vs voltage plot?
outward: conductance of outward currents is greater than for inward currents (curves the slope upward)
inward: conductance of inward currents is greater than for outward currents (curves the slope downward)
what kind of channel is K+? when is the conductance of the channel high and when does it decrease?
inward rectifier
conductance is high when the cell is hyperpolarized
it decreases as cell depolarizes
other than the permeability of the channel, what does current flow rely on?
electrical and ionic concentration gradients
describe the molecular structure of a mammalian potassium channel.
channel is made up of 4 identical subunits whose transmembrane domains form a pore that crosses the membrane. it selectively filters out ions other than potassium.
how do ions cross a channel?
passively, in single file by electrodiffusion
what do channel blockers do and what is the physiological effect of calcium channel blockers?
channel blockers occlude channels on the extracellular side
calcium channel blockers reduce heart rate and contractility, lowering cardiac output and blood pressure
what causes the depolarization of a muscle cell? why?
increase in the relative permeability of sodium to potassium. this is becausethe sodium gradient now has a much larger effect on the voltage than at rest
what is the resting potential of a cardiac muscle cell?
-60 mV
how much does the internal concentration of sodium change during an action potential?
not very much
what is an overshoot? what does this indicate?
when an upstroke goes beyond zero to positive potential. this indicates that there is an inward directed positive ion gradient (Na+) rather than an outwardly directed positive ion gradient (K+) dominating voltage
what are the three states of voltage-gated sodium and calcium channels?
closed (resting), open (active) and closed (inactive)
what type of channels are sodium and calcium channels? when are their conductances low and when do they increase?
outwardly rectifying
conductances are low at hyperpolarized voltages, they open up at a threshold level of membrane depolarization (much higher conductance during the upstroke)
why do calcium and sodium enter a cell when the voltage inside is positive?
because the inward concentration gradient force predominates over the outwardly directed electrical force
what triggers inactivation of sodium channels? how is this accomplished?
they spontaneously inactivate rapidly after they are opened
the inactivation gate occludes the cytoplasmic side of the channel by conformational change
which is faster: the rate of inactivation of sodium or calcium channels?
sodium
how does a sodium channel progress from inactive to resting?
the h gate (cytoplasmic) opens and the m gate (extracellular) closes
what do sodium and calcium channels depend on?
time and voltage
what is the absolute refractory period?
the time during which an action potential cannot be generated, no mater how strong the stimulus
what is the relative refractory period? why does this occur?
the time during which only a very high stimulus will generate an action potential
occurs because only some of the channels have returned to the resting state
when does the refractory period occur in the cardiac cycle? why?
during diastole to allow the heart to refill before the next contraction
what happens when a resting potential is more depolarized than usual?
some of the channels will be inactivated so the action potential will be smaller and slower than normal
what happens if the stimulating voltage threshold has a slower upstroke than usual?
some of the channels will inactivate and the action potential will be smaller and with a slower upstroke
what can be a result of abnormally small action potentials with slow upstrokes?
certain arrhythmias
what causes the opening of K+ channels? what implication does this have?
charged transmembrane domains move when the transmembrane voltage becomes more positive and the channel opens
causes conductance to be higher at depolarized than at hyperpolarized voltages and the currents are outward
when are delayed outwardly rectifying K+ channels used and when are inwardly rectifying iK1 channels used?
iK1 channels maintain the internally negative resting potential
delayed outwardly rectifying K+ channels repolarize the cell
what is a dendrogram and what does it indicate for ion channels?
dendrogram-chronological map showing the molecular evolution of ion channels
shows how many sub types of channels have evolved and why Ca and Na channels are more closely related than K channels (same branch)
which type of channel has the most subtypes?
potassium channels
T or F: Different cells each have their own subtype of the major ion channels.
F. Different cells may have different subtypes, but more than a few subtypes of the same ion channel may coexist on the same cell
why do different subtypes of the same channel exist on the same cell?
because separate voltage, time dependancies and rectification properties mold the action potential to fit the needs of the cell
why is there a delay in the opening of the outward rectifier K+ channel during an action potential?
because it permits a finite duration for the depolarization phase of the action potential
how is the delayed outward rectifier K+ channel deactivated?
a “ball and chain” mechanism swings a domain on the cytoplasmic side to occlude the channel
how does the voltage change during the different phases of the action potential?
the voltage moves toward the equilibrium potential of the most conductive ion
what are the phases of action potentials in the atrium, the bundle of HIS, the Purkinje network and he ventricle?
sodium dependent upstroke, calcium dependent plateau and potassium-dependent repolarization
what is the difference between the phases of action potentials in the SA and AV nodes?
the SA and AV node potentials have smaller calcium dependent upstrokes and potassium dependent repolarization
NO SODIUM CONTRIBUTION
what is responsible for the automaticity of the heart rhythm?
the SA node pacemaker potential has a spontaneously depolarizing ramp depolarization
what is the difference between the shape of action potential in cardiac muscle compared to skeletal muscle?
skeletal muscle duration is much shorter (few msec vs 300-400 msec)
phases 1 and 2 do not have clear counterparts in nerve and skeletal muscle
repolarization is triphasic in cardiac muscle and monophasic in skeletal muscle
what does having a triphasic repolarization mean?
after the initial upstroke, the membrane voltage starts to go down then goes up again briefly before going to the resting potential
which action potential in the heart is the largest? what is it?
Purkinje Fiber action potential
can be >120 mV (resting potential is -90 mV and overshoot can reach +30 mV)
describe the length of the action potential and refractory period in Purkinji fibers. why is this the case?
long duration of action potential with long refractory period.
long refractory period prevents the ventricular muscle next to it from reactivating the conduction system
what causes the plateau of voltage during the action potential of a purkinji fiber?
during the early phase of the plateau, inward Ca and outward K currents are appropriately balanced. both currents decline during the plateau phase.
what causes repolarization of the purkinji fiber?
delayed rectifier currents
what are the phases of the Purkinji action potential and what are the causes?
Phase 0: upstroke, fast inward sodium current, rapid inactivation (iNa)
Phase 1: transient repolarization from outward K currents (ito1, ito2)
Phase 2: plateau, slow outward K (iKr, IKs, iKCa) current and slow inward calcium current (iCaL), slow inactivation
Phase 3: repolarization, delayed outward rectifier potassium currents (iKr and IKs)-r is rapidly activating and s is slow
Phase 4: resting potential, inward rectifier potassium currents (iK1)
what causes the opening of the L-Type Ca channels?
depolarization from the sodium channels opens the L-type calcium channels
when do the T-type Ca channels open in Purkinje Fibers and when are they important?
open transiently during depolarization (small current overshadowed by Na)
important contributing to generation of pacemaker currents in SA node
where is the initiation site of cardiac excitation and what is its rate of action potential firing?
the SA node
60-100 beats/min
describe the phases of SA node action potentials.
Phase 0: rapid depolarization due mostly to iCa via voltage dependent L type channels
Phase 3: slower repolarization phase due to inactivation of iCa mostly and activation of voltage dependant iK
Phase 4: slow ramping depolarization because of activation of iF
what does pace maker activity arise from?
T-type Ca channels, iK and a current iF (the pace maker current)
what is iF?
the pace maker current that is a net inward current that activates in response to hyperpolarization (instead of the usual depolarization)
has both an inward Na and outward K component
what are the differences between the L type Ca channel and the T type Ca channel?
L type activated when the cell is more depolarized than the T type channel. L type is slowly inactivated and large, T is quickly inactivated and small.
what are three mechanisms that can slow the SA node pacemaker?
decreased rate of diastolic depolarization, decreased hyperpolarization (more negative), and increased threshold for a new action potential
how is pacemaker activity at the SA node regulated to slow the heart?
PSN inhibition by vagus nerve (vagal break): ACh, muscarinic (M2) receptor (metabotropic)- decreases cAMP
ACh also opens a K channel to hyperpolarize the heart
how does SNS regulate the heart rate?
norepinephrine, beta1 adrenergic receptors, activate Gs and adenylyl cyclase. increases heart rate
what do the changes mediated by the SNS do to increase the heart rate?
increase phase 4 steepness by increasing inward iF and inward iCaT
puts the threshold of iCaL at a more negative value (less depolarization needed to activate it)
what remains unaffected with sympathetic stimulation of the heart?
maximum diastolic potential (lowest potential) is unaffected
what has a greater effect on the heart, the PNS or SNS? how do we know this?
parasympathetic because removing the PNS interaction with the heart the beat increases rapidly, but by removing the SNS interaction, heart rate drops minorly
what would the heart rate be if there were no sympathetic or parasympathetic control? what does this demonstrate?
100 beats/min
shows that the PNS has a greater influence on the heart beat
what are the names of some cardioselective beta blockers and what do they do?
atenolol and propranolol
block beta one receptors to induce bradycardia
what agent affects muscarinic ACh receptors and what is its effect?
atropine
block M2 and induces tachycardia
what does sarin do?
inhibits accetylcholinesterase and induces bradycardia
what are the effects of antidepressants like Prozac and Elavil on heart rate?
they block the uptake of norepinephrin and increase heart rate
what are the first three phases of the atrial muscle action potential?
Phase 0: rapid depolarization that overshoots, due to iNa
Phase 1: small repolarization, activation of iTO, decreased iCa and iNa
Phase 2: short plateau of depolarization due to prolonged iCa plus iKur (ultrarapid)-currents balance each other
what are the last two phases of the atrial muscle action potential?
Phase 3: repolarization, inactivation of iCa and increased iK
Phase 4: resting potential due to increased iK1 (no depolarization ramp)
what is the difference between the SA node action potential and atrial action potential that causes pacemaker function?
iF
what is the consequence of the plateau phase 2?
Ca entry promotes contraction, refractory period permits filling
what are some differences between the action potentials in the Purkinji Fibers and in the atria?
the atria has a smaller action potential with a shorter plateau
where do action potentials for the atrial muscle cells come from and how do they travel?
come from the SA node and travel via gap junction coupling
how is the atrial muscle modulated by the ANS?
little parasympathetic modulation, responds to SNS input and circulating epinephrine
what action potential is similar to that of the SA node? why is this so?
the AV node
because the AV node cells have intrinsic pace maker activity
how long does it take for an action potential to travel from the SA node to the AV node? what is the frequency of action potential firing in the AV node?
30ms
40/min
what is the delay stage between atrial and ventricular contraction?
90 ms
what are some characteristics of AV conduction?
calcium dependent upstroke-small and slow
high internal resistance of small diameter cells
relatively few gap junctions
conduction velocity low
what are the effects of the ANS on the AV node?
PNS- decreased firing rate, decreased conduction velocity (slows depolarization)
SNS- increased firing rate, increased conduction velocity
what cells have the highest conduction velocity in the heart?
bundle branches and Purkinje Fibers
what is the major difference between the action potentials of muscle cells and purkinje fibers?
purkinji fibers have a pacemaker current iF
describe the intrinsic firing of purkinje fibers.
intrinsic firing rate is less than 20/min and it is irregular
what are the action potentials in the ventricle similar to?
the action potential of the atria
describe the spatiotemporal characteristics of ventricular activation. what does this sequence accomplish?
apex activated first from endocardium to epicardium
rapid transfer to the base by the purkinji fibers
produces efficient ejection of blood
how are the action potentials different in the layers of the ventricular wall?
repolarization length is the major difference. fastest in epicardium, then endocardium and m cells are the slowest
how is coordinated cardiac contraction achieved?
wave of electrical excitation
contraction coupled to the excitation
heart consisting of two electrical syncytia
how are cardiac action potentials propegated?
electrical snapses- gap junctions
what is the threshold for initiation of a propagated cardiac action potential?
-75 mV
how are gap junctions opened and closed?
by the movement of the six transmembrane subunits along each other to either create a pore or occlude the opening
why is the heart described as a syncytium of cells?
a syncytium is a multinucleate cell that arises from the fusion of many other cells. it is described as such because gap junctions allow easy communication throughout the heart
describe the summary of depolarization of the heart muscle.
atria-> septum from left to right-> anteroseptal region towards the apex-> posterior portion of the base of the left ventricle-> bulk of myocardium from endocardium to pericardium
do all electrical conducting cells in the heart have a pacemaker discharge?
yes
describe the summary of activation of the heart.
SA node-> atrium-> AV node-> AV bundle-> bundle branches-> purkinje network-> ventricle
