Cardiac Electrophysiology (B 2 : W 1) Flashcards
What is the resting membrane potential of a cardiac ventricle?
-90 mV
What is the significance of the shape of the action potential in a cardiac ventricle?
The shape of the action potential has an effect on the amplitude of contraction
- It is very long
- One AP –> One contraction
What is the sequence of events associated with ventricular action potential?
Electrical activity precedes physical activity
Electrical event –> chemical activity –> mechanical event
During cardiac cycle, there is a decline in ventricular pressure as AP repolarizes (T wave)
Compare action potential between nodal cells (SA and AV) and chamber action potentials (atria and ventricles)
- In SA and AV nodes
- Slow upstroke velocity
- Depolarization is slow
- Threshold is more positive
- In atrial and ventricular cells
- High amplitude
- Fast AP
- In atria: want contraction to be quick and homogenous
- In ventricles: endocardium is excited first, and then goes across ventricular wall
- Slow repolarization
What is the difference in resting potentials of SA action potentials and ventricular action potentials?
- SA RMP sits at about -50 mV
- Pacemaker cells have unstable resting potential that goes up and down
- Ventricular RMP sits at -85
- Very stable RMP
- AP is higher than it is in SA node
- Without impulse from SA node, it will not depolarize
Why is the SA node the dominant pacemaker over the AV node?
SA has a faster slope of depolarization than the AV node, and thus is the dominant pacemaker
- Impulse from fast SA pacemaker reaches AV node cell and causes faster membrane depolarization
- If no impulse is coming to AV node, slower depolarization takes longer
- AV is entrained because of the impulse it receives from SA
What does the Nernst equation tell us?
Determines the energy needed to maintain ion gradient in the system.
Takes into acount chemical gradient and electrical gradient
At equilibrium potential, there is no net flux of the ion
How do ions particpate in the generation of a membrane potential?
Flux of ions generates membrane potential
Need ion channels to produce this flux - can’t go through the lipid bilayer on their own
What is the dominant ion to determine the membrane potential of ventricular cells and Purkinje cells?
Potassium
Membrane is highly permeable to potassium
Since the resting membrane potential of most cardiac cells does not equate to Nernst potentials of any of the ions, what does this mean?
This suggests that the cardiac cell membrane is permeable to more than one type of ion.
We now know that the “resting” (diastolic) cardiac membrane is maily permeable to K, but also displays some permeability to Na.
Contrast permeability ratio of Na:K in pacemaker cells and non-pacemaker cells
- Non-pacemaker cells (atrial, ventricular, Purkinje) exhibit a low permeability ratio of Na:K (1-3 : 100)
- More polarized
- More negative RMP
- Pacemaker cells (SA and AV node) display a relatively higher permeability ratio (1 : 5-10)
What does the GHK (Goldman-Hodgkin-Katz) equation tell us?
Takes into account the electric and chemical gradients for more than one ion in a cell
Describe the plots on this graph
- Black: No Na permeability; linear plot
- Red: Relative permeability of Na is 0.02
- When K reaches a high concentration, there is no more membrane potential - intercept
- K channels at rest are sensitive to the K concentration outside of the cell
- K permeability goes down dramatically
- Membrane potential tends to go to Na - depolarize at this point
- Low K means danger in ventricular cells - can induce arrhythmias
What is the function of the electrogenic Na-K pump?
- Maintains the gradient
- Contributes to resting membrane potential
- By as much as -10 mV
What is the function of the aqueous pore in a voltage-gated (dependent) ion channe?
The pore lowers the energy barrier by dissolving ion across membrane
- Narrow selectivity filter - only allows some through
- Conducts millions of ions per second when they are open
- Some are activated by depolarization, some by hyperpolarization
What is the role of voltage-gated Na and K channels in generating the action potential in axons?
Conductance = flux = channels open
- Na conductance is low at rest
- Na conductance increases above K during action potential
- Na goes down on its own, K goes up and causes repolarization
Describe the phases of typical cardiac action potentials?
- Resting potential is phase 4
- Excitation coming upstream from cell causes a little “foot” of an action potential
- If it reaches threshold, it depolarizes - phase 0
- All or none
- Cannot be interrupted
- Wants to reach the ENa but K channels are opening and opposing it
- Phase 1 - inactivation of Na channels, activation of Ca channels
-
Phase 2 is the plateau
- Characteristic of cardiac cells
- Ca current in matches K current out
-
Phase 3 is rapid repolarization
- Ca channels inactivated
What is one important difference between action potentials in neurons and cardiac cells in regards to PK?
- In neurons, PK goes up during the action potential
- In cardiac cells, PK goes down
This, and the fact that cardiac cells have a prominent Ca current, is the reason for the existence of a long plateau
Describe the phases of SA nodal action potentials
- Phase 0: Ca channel produces Ca current to cause action potential
- Channels open at - 40 mV
- Ca channel desnity is low
- Not much amplitude because of few Ca channels
- Phase 3: peak of AP opens K channels - repolarization
- If current = pacemaker current
- Nonselective channel permeates both Na and K
- Pacemaker current starts to depolarize until threshold is released
How do local circuit currents mediate propagation?
- Local circuit currents are transmitted across a distance
- Can depolarize a neihboring region
- Excite passively
- Domino effect
- More complicated in cardiac cells because of 3D structure than it is in nerves
- Same principle guiding propagation
What is the impact of high K on action potentials?
- Slower response because of K
- True slow response
- Slower depolarization
- Slower downstream cell depolarization
- Slower conduction velocity in general
What is the difference between the absolute/effective refractory period and the relative refractory period?
- Absolute refractory period
- Cannot trigger a premature contraction
- Relative refractory period
- Abnormal stimuls here could cause premature excitation
- Could lead to depressed response - Na channels not fully available
- AP will have lower response
What are the three mechanisms for altering pacemaker activity?
- Change the slope of phase 4 diastolic depolarization
- Increase - Faster AP
- Decrease - Slower AP
- Change in threshold potential
- Lowering threshold accelerates pacemaker activity
- Change in maxium diastolic potential
