Cardiac Electrophysiology Flashcards
how does the action potential of nodal cells differ from that of myocytes
greater resting potential (not as negative- much less hyperpolerization), baseline is drifting (not stable), no fast inward current (no voltage gated sodium channels- slower rate of rise), no plateu phase
Which phase is absent in nodal cell action potentials
No phase 2 (also have a very slow phase 0)
Components of the membrane clock
1.) Calcium current (L and T type channels) 2.) Potassium current 3.) Funny current (pacemaker current) 4.) Electrogenic transporters (INCX and NaKATPase)
what is the pacemaker current and what is its major role
Funny current - Mixed Na and K inward current - protects against hyperpolarization and prevents excessive bradycardia
dual activation of funny channels
1.) Hyperpolarization 2.) Cyclic nucleotides (cAMP)
at what voltage do funny channels activate
activates at - 55
describe the relationship between funny current and membrane potential
the more negative the membrane potential the greater the current
what is MDP
Maximum diastolic pressure aprox -60 mV in the SA node
Phase 4 of nodal action potential
Diastolic depolarization - carried out by funny current leading to threshold . Gradual increase in Na influx through Na channels. T-type Ca open to bring the membrane to threshold which leads to opening of L-type Ca channels
Calcium Clock
generation of calcium “sparks” - occur spontaneously and at a slowly increasing rate that peaks at the onset of action potential
Calcium “sparks”
intracellular releases of Ca from SR duriing diastole - local calcium release = ticking of the clock (critical for automaticity) NOT RESPONSIBLE FOR EXCITATION COUPLING
what links the clocks of pacemaker cells
Na Ca exchanger - gets activated by local calcium release
Keys to automaticity
1.) Calcium sparks 2.) Na Ca exchanger (INCX) 3.) Andenylate cyclase (high phosphorylation state)
Role of adenylate cyclase
induced by calcium and results in high phosphorylation state of nodal cells - critical for pacemaker function and control (favors calcium reuptake and release)
Ryanodine channels
regulate the release of calcium- rate of release is regulated by the phosphorylation state of ryanodine
SERCA
regulates the reuptake of Ca. Activity determined by the balance between P-Phospholambam and Phospholambam (more P-Phospholambam = more reuptake and faster relaxation)
Phospholamban
inhibits SERCA and therfore Ca reuptake
lusitrophy
refers to myocardial relaxation (uptake of Ca by SERCA is positive lusitropic effect)
Phase 0 of nodal cell action potentials
depolarizing current carried mainly by Ca channels ( Ca influx) in response to membrane depolarization
Phase 3 of nodal cell action potentials
decreased Ca influx and increased K influx responsible for depolarization
why is the plateau phase missing in nodal cell action potentials
significantly greater It01 in pacemakers than in myocytes which rapidly overcomes inward Ca current and leads straight to phase 3
roel of Na K ATPase in nodal cells
ensures the Na and K gradient do not get disrupted by accumulations and losses after action potentials (accumulate Na, lose K)
why is signal delayed in the AV node
ensures atrial contraction is complet before ventricle contract
hallmarks of true pacemaker cells
1.) Unstable membrane potential which spontaneously depolarizes to threshold 2.) Rhythmicity 3.) dictates heart rate
SA node (location, pacing rate)
located near the base of the right atrium - pacing rate 60-100 bpm. Primary pacemaker for cardiac conduction
what modulates the rhytmicity of the SA node
autonomic nervous system
AV node location and pacing rate
located at the junction of the right atrial septum and the interventricular septum - 40-55 bpm
Bundle of His and bundle branches
His = 40-55 bpm Branches = 25-40
conduction velocity of the bundle branches
Right bundle branch is smaller in diameter and has slower conduction velocity, Left branch- wider diameter faster conduction velocity – both end up uniform
Overdrive supression
Subsitiary (potential) pacemakers are driven at a highter rat thant their own and their excitability is reduced resulting in large uptake of Na. This causes and increase in Na-K ATPase activity resulting in relative hyperpolarization and more stable baseline - aka supressed automaticity
normal activation sequence of the heart
depolarization of SA node, conduction through atria, AV nodal delay, rapid conduction through purkinje system
Principle site s of delay through the AV node
AN and N region with N being the slowest - Basis for the PR interval
relationship between heart rate and AV node conduction
Increase in heart rate results in decrease in AV node conduction ( protects the ventricles from excessive activation)
where is the fastest conduction velocity of the heart
Purkinje fibers (can depolarize the entire ventricle almost immediately)
direction of depolarization
endocardium to epicardium
conuction velocity of purkinje fibers
2-4 m/s
Impact of Hyperkalemia on pacemaker action potentials
becomes lesss negative and the rate of rise, amplitude, and duration of the action potential decrease
impact of Hypokalemia on pacemaker action potentials
reduce Vm (more negative) therefore hyperpolarizing the cells leading to delayed action potentials and possible arrythmias. Will have increased heart rate and increased refractory period as well
impact of hyponatremia on pacemaker action potentials
minimal due to low leak conductance. Phase 0 is reduced by excitation is not diminished until VERY low levels
Ryanodine
inhibitor of CA release from SR (reduces local calcium releases- loss of calcium spark)
Sick Sinus Syndrome
mutations in either funny channels or the Na Ca exhanger resulting in altered current which impedes normal diastolic depolarization. SA nodal impulse recovery is impaired and hyperpolarization leads to bradycardia and reduction of intrinsic rhythm and max heart rate
Bowdich effect
increase in chronotropic is usually accompanied by increased ionotropic (increased rate goes with increased contractility) why? Linking the calcium clock with the membrane clock
impact of catecholamine on the refractory period
shortens the refractory period by accelerating the onset of phase 3 repolarization (through phosphorylation of K channels)
ionotropic effect of sympathetic activation
positive ionotropic
ionotropic effect of parasympathetic actionvation
negative ionotropic
heart rate is determined by what interval- describe variability
R-R interval. Some variability is good - balance - arrythmias are an expression of excessive variability and heart failure is an expression of low variability
decreased conduction velocity in the AV node gives rise to what
heart block
decreased conduction velocity in other regions of the myocardium (outside AV node) give rise to what
recurrent arrythmias
decremental conduction
abnormally slow conduction that fials to reach threshold and fails to result in depolarization of the next cell therefore resuling in blocked transmission
conditions for reentry
1.) Closed conduction System 2.) Regions of unidirectional conduction block (decremental conduction block) 3.) Transit time > refractory time (gives it time to turn back around and go the other way)
in general what mechanism prevents reentry
refractory period (if we change it we are at risk for reentry and arrhythmias)
Flutter (mechanism)
self sustaining wave of excitation that passes endlesslu around the atria or ventricle - moves as asingle UNIDIRECTIONAL impulse
Fibrillation (mechanism)
totally chaotic pattern of excitation results in complete loss of pump function
Circus movement can lead to fibrillation under the following conditions
1.) Irregular blocking of impulses (some blocked, some transmitted) 2.) Rapid stimulation (leads to slow conduction and/or increased refractory) 3.) blocked impulses divide and propogate in two differnet paths around the block leading to a chain reaction
