SM 113a - Normal Cardiac Electrical Activity Flashcards
List the 3 factors that contribute to the plateau of the cardiac action potential
- The cell is permeable to Ca2+ due to ICa (L-type channel)
- IK1 is blocked; K+ cannot get out
- IK is slow; it only begins to contribute to K+ outflow near the end of the plateau (phase 3)
In the SA Node, which current is responsible for phase 3?
K+ channels open
K+ flows out of the cell, hyperpolarizing it. L-type Ca2+ channels close
Which ions have a negative equilibrium potential?
K+ and Cl-
Describe the steps that occur in repolarization (phase 3)
In general: ICa-L gradually inactivates, and IK activates
- The f gate closes, halting inward Ca2+ flow (inactivation)
- Vm becomes more negative
- Inward rectification by IK1 is decreased (less K+ in)
- K+ outflow increases via IK1 (no longer blocked)
- IK becomes more active as Vm becomes more negative
- IKs = slow
- IKr = rapid
- IKur = ultrarapid
Which ion is responsible for the “slow response only” cardiac action potential?
Describe some of the characteristics of this kind of action potential
Ca2+ (when INa is inhibited/inactivated)
Compared with an INa phase 0 upstroke, a Ca2+ driven upstroke will have…
- Slower time dependency of activation and inactivation
- Slower upstroke velocity
- Slower conduction velocity between cells
- Lower safety margin - this decreases the probability of successful propagation between cells
- Longer refractory period = longer action potential duration
Which ions have a positive equilibrium potential?
Na+, Ca2+
What is the mechanism of fast response action potentials vs slow response?
Under what conditions does each type of action potential occur?
Fast response APs are governed by INa. These occur under normal contitions in most cells
Slow response APs are governed by ICa-L. These occur if the resting membrane potential is not negative enough to activate INa, such as in pacemaker cells
For example, at a resting membrane potential of -60 mV, the m gate for the Na+ channel is open, but the h gate is inactivated. At this voltage, the d and f gates for Ca2+ may open, but they are slower. The result is a longer, less powerful action potential.
What is the equation to calculate resting membrane potential using conductance?
Note: if other ions have significant conductance for a particular cell, add them as well
Which current drives phase 0 in cardiomyocytes?
- INa into the cell through rapid Na+ channels
- Controlled by m (activation) and h (inactivation) gates
- Supported by ICa into the cell through slow L-type Ca2+ channels (but these are slower and more active in phase 2)
- Controlled by d (activation) and f (inactivation) gates
What are the 3 types of dependencies that a membrane channel may have?
Voltage dependence
Time dependence
Ligand dependence
Which cells in the body exibit the following action potential?
Cells with pacemaker activity
- SA Node (Primary pacemaker)
- AV Node
- Bundle Branches and Purkinje Fibers
Under what conditions would Ca2+ be responsible for the phase 0 upstroke?
If INa is inhibited
(potentially due to leaky K+ channels resulting in less negative Vm)
Which current is responsible for phase 1?
Ito
Transient outward K+ current
In a typical cell at baseline, which ions typically have the highest conductance?
Na+, K+
In the SA node, which mechanisms are responsible for phase 4?
- If, or “Funny current” that carries Na+. Sodium leaks into the cell, depolarizing it to the threshold potential.
- K+ channels are closed/less active
-
Na+/Ca2+ exchanger is activated due to the release of Ca2+ from the sarcoplsamic reticulum, via RyRs.
1 Ca2+ out for 3 Na+ in = Net inward Na+ current - As the pacemaker cell gets closer to the threshold potential, t-type Ca2+ channels open. Ca2+ rushes in, and threshold is reached
Which current is the main driver of resting membrane potential (phase 4)?
IK1 - The inward rectifying current
Note: IK1 is not active in the plateau phase (phase 2). Flow of K+ out of the cell through the inward rectifying channel is blocked (maybe by Mg2+); K+ cannot flow out via IK1 to repolarize the cell
Which K+ currents contribute to both repolarization in phase 3 and resting membrane potential in phase 4?
IK - a combination of K+ currents
- IKs = slow
- IKr = rapid
- IKur = ultrarapid
What is the Nernst equation for a cation?
(Note: [ion]out is in the denominator and [ion]in is in the numerator for anions)
Which current drives phase 2?
ICa flows in (and K+ does not flow out)
The L-type Ca2+ channels remain open, allowing Ca2+ to flow into the cell. This keeps the Vm of the cardiomyocyte positive
K+ does not flow out to repolarize the cell because…
- IK1, the inward rectifier current, is closed
- Inward rectifier = ions flow in more easily than out
- Mg2+ sits on the intracellular side, blocking K+ outflow
- IK, through the rectifier channel is slow to activate; it does not play a role until phase 3
Which current drives phase 3?
IK is active (and ICa-L gradually inactivates)
INa is controlled by m (activation) and h (inactivation gates)
Describe the state of the m and h gates at each phase of the cardiac action potential
What current is responsible for phase 0?
Increased Ca2+ conductance through L-type Ca2+ channels
How is phase 4 in the pacemaker cells (shown) different from phase 4 in ventricular myocytes?
In pacemaker cells, the membrane is slowly depolarizing in phase 4 due to If, or “funny current” that allows Na+ to leak into the cell, T-type Ca2+ channels, and Na+/Ca2+ exchanger activity.
In ventricular myocytes (and all other non-pacemaker cells), phase 4 is flat becuase there is no current that depolarizes the cell automatically. Changes to membrane potential occur only in response to stimuli (such as nearby action potentials).
