Flashcards in Cardiac Excitation Deck (43)
How is the heart innervated?
Largely parasympathetic of atria, SA, and AV node, but not ventricles
sympathetic of atria, SA and AV node, and ventricles
What are the phases of ventricular action potential?
4- resting phase (-85mV)
0- beginning of action potential
1- small decrease
2- plateau phase
What is the resting potential maintained by?
The principal active channel during the resting phase is Kir2.1 (aka K1), assisted by two other K channels (IKATP and IKAch). These channels set the resting potential at close to the K reversal potential, i.e. about -85 mV.
What causes phase 0?
Phase 0 is induced by rapid Na channel activation (inward current shown by downward yellow tracing), simultaneously with K channel inactivation (up to +20mV).
What causes phase 1?
However, this is transient and is followed by activation of Ito channel activation (transient outward K channel; all K channels are shown in green) which slightly repolarizes the cell membrane during phase 1
What causes phase 2?
During Phase 2, a voltage dependent inward Ca2+ current is balanced by 3 outward K+ currents (Ikur, Ikr and Iks). Lasts about 400 ms
What causes phase 3?
Reactivation of K1 at the end of phase 2, together with reactivation of two other K channels (IKATP and IKAch) induces repolarization of cells (phase 3). It is important to note that Na channels need to have a potential close to -85 mV in order to “reset” for the next cardiac cycle.
What other channels exist in the atria and nodes?
there are two other channels, one of which is inhibited by ATP and when the ATP:ADP ratio drops, the channel activates and the channel can help with re-polarization
The other channel is sensitive to ACh and is important in regulating the SA and AV node potentials
How do fast Na channels work?
The channel has two gates activated at different voltages. The V gate opens at membrane potentials more positive than -40 mV, whereas the inactivation gate opens at membrane potentials more negative than -65 mV. At rest, the V gate (V for voltage) is closed because the cell membrane is at the resting level (-85 mV). However, the inactivation gate is open because the channel is experiencing a voltage of -85 mV.
When cells reach the threshold potential, the V gate opens rapidly before the inactivation gate has time to close. This allows Na influx to occur and to rapidly further depolarize cells in a feed forward manner (both gates are open and more gates open as the membrane voltage becomes more positive).
A few milliseconds later, the inactivation gate swings shut, because of the positive membrane potential.
Eventually, when the cells repolarize in phase 3, the V gate closes whereas the inactivation gate opens.
In sinoatrial cells (pacemaker cells), the fast Na channel is permanently in the inactivated state because of the relatively more positive resting membrane potential in these cells, which keeps the inactivation gate closed.
Defective Na channels lead to what?
What is the maximal negative membrane potential in SA node cells?
-65 mV, as compared to -85 mV in ventricular myocytes.
What is the resting membrane potential in SA node cells?
unstable. This is due to the fact that these cells have an inward Na+ current (known as the “funny” current) which is activated by NEGATIVE membrane potential (i.e. during re-polarization), unlike the fast Na current which is activated by POSITIVE membrane potential.
Are there a lot of fast NA channels in SA cells?
No, there are few fast Na channels active in SA cells because the relatively positive membrane potential (-65 mV) suppresses fast Na channel “resetting” event which needs a membrane potential more negative (-85 mV) than the cells provide
Is there a 'plateau' phase for SA cells?
No, there is no plateau phase for SA node cell action potential
What else is different about the action potential of SA cells vs ventricular myocytes?
Fifthly, note that in ventricular myocytes, K channel activity is decreased during phase 2 but is not zero, due to activation of several K channels with low activity, thus balancing the inward Ca current, and causing the plateau phase in ventricular myocytes.
What happens when Na+ influx via funny current in SA cells causes depolarization to about -40mV?
voltage dependent calcium channels open (called T channels)
Ca channels that open late during the pacemaker potential are T-type channels that open and then close rapidly. At the threshold, L-type Ca channels open. The slope of the action potential is less steep in these cells than in ventricular cells because Ca channels are slower in conducting current than are fast Na channels that open in ventricular cells. At the peak of the action potential, Ca channels begin to close and delayed rectifier voltage-gated K channels begin to open.
What is the absolute refractory period?
The absolute refractory period is the time when no stimulus, regardless of strength, can induce an action potential. This is dependent on refractory fast Na channels. Exists from phase) to about midway into phase 3
What is the effective refractory period?
The effective refractory period is the time when no stimulus generated by surrounding cells can elicit an action potential. Exists from phase 0 to further into the phase 3 re-polarization
What is the relative refractory period?
The relative refractory period is the time when a very strong stimulus can elicit an action potential that is weaker than a normal action potential. Exists from end of ARP to close to -85 mV
the action potential here will have a smaller positive slope than normal because not all Na channels are reset yet
What is the supranormal period?
The supranormal period is the time when a weaker than normal stimulus can elicit an action potential. The SNP is dependent on refractory K channels that have not fully activated and thus are unable to clamp the resting voltage in the face of a stimulus (cause of arrhythmia)
Exists right as re-polarization occurs
What sets the heartbeat?
the SA node has the highest rate of spontaneous discharge and thus normally sets the rate of the heartbeat
What sets the heartbeat if the SA node is defective?
The next lower discharge rate belongs to the AV node which can become the pacemaker in the event of an ineffective SA node pacemaker.
Moreover, in the event of complete heartblock, i.e. no conduction across the AV node, the bundle of His or Purkinje cells can assume the role of pacemaker, albeit at rates that are not adequate in the long term.
Sympathetic and parasympathetic efferent nerves emanate from two different areas of the medulla. What determines the levels of sympathetic drive? What determines parasympathetic drive?
the cardioacceleratory center
the cardioinhibitory center
How is sympathetic activity transmitted to the heart? Parasympathetic?
sympathetic activity is transmitted via the sympathetic cardiac nerve which influences the SA node, the AV node and the ventricular cells.
Parasympathetic activity which is transmitted via the vagus nerve influences the SA and AV nodes but NOT ventricular cells
What is parasympathetic action in the heart dependent on?
activation of K channels and inactivation of Ca2+ channels
What are some ways parasympathetic activity can decrease the action of SA node cells (and decrease HR)?
- decreased If (funny) current by decreasing cAMP
- more negative maximal diastolic potential “MDP”, mediated by increased K channel activity (via ACh).
- increased threshold for Ca opening via decreased cAMP levels
How does depolarization begin in the heart?
Starts at SA and goes to the AV node in just a few milliseconds
How long does it take for the depolarization wave to cross the AV node?
40 milliseconds (para/sym drugs affect this- so remember that CV drugs not only influence induction but conduction as well)- then to the bundle of His
Once in the bundle of His, the speed of conduction picks up again
What is dromotropy?
increased speed of conduction