Why do Beta Blockers (Class II Antiarrhythmics) decrease slope of Phase 4?

[warriorinthemaking]

Hey all,

So I'm reading FA 2017 and it says that the mechanism of class ii antiarrhythmics (beta blockers) decrease SA and AV nodal activity by decreasing cAMP and thus Ca++ currents, thereby decreasing the slope of Phase 4 and making it harder to depolarize the cell into action potential.

Phase 4 is when the funny current of mixed Na+ and K+ enters the cell to depolarize the cell membrane; Ca++ has nothing to do with it to my knowledge. So why would it affect Phase 4. More importantly why is Phase 0 not affected, in which Ca++ current is directly responsible for the depolarization of the pacemaker cell?

Bonus: why is repolarization prolonged with beta blockers?

---

Members don't see this ad.

 

[Lnsean]

Hey all,

So I'm reading FA 2017 and it says that the mechanism of class ii antiarrhythmics (beta blockers) decrease SA and AV nodal activity by decreasing cAMP and thus Ca++ currents, thereby decreasing the slope of Phase 4 and making it harder to depolarize the cell into action potential.

Phase 4 is when the funny current of mixed Na+ and K+ enters the cell to depolarize the cell membrane; Ca++ has nothing to do with it to my knowledge. So why would it affect Phase 4. More importantly why is Phase 0 not affected, in which Ca++ current is directly responsible for the depolarization of the pacemaker cell?

Bonus: why is repolarization prolonged with beta blockers?

Phase 4 of the nodal action potential consists of inward Ca channels (T-type) as well as funny Na channels. There is also a bit of K current as well i think.

 

[FindersFee5]

Phase 4 of the nodal action potential consists of inward Ca channels (T-type) as well as funny Na channels. There is also a bit of K current as well i think.

Correct. It also doesn't affect phase 0 because those are L-type channels (which are acted on by non-dihydropyridine calcium channel blockers, type 4 antiarrhythmics)

 

[warriorinthemaking]

Interesting - so I guess I was getting confused because the sympathetic nervous system uses beta1 receptors to stimulate cardiac myocytes (not pacemakers) to keep L-Type Ca++ Channels open and thus increase contractility. However, when the Symp NS affects the pacemaker cells, it does not affect L-Type Ca++ Channels but rather T-Type Ca++ Channels to reach action potential faster and speed up heart rate. This makes sense because it's that Phase 4 climb that really stalls cells when it comes to heart rate, particularly at the AV Node. Changing Phase 0 would help but not nearly as much as it changing Phase 0, it seems to me.

Now for the big one: why do beta blockers affect repolarization?

 

[Lnsean]

Interesting - so I guess I was getting confused because the sympathetic nervous system uses beta1 receptors to stimulate cardiac myocytes (not pacemakers) to keep L-Type Ca++ Channels open and thus increase contractility. However, when the Symp NS affects the pacemaker cells, it does not affect L-Type Ca++ Channels but rather T-Type Ca++ Channels to reach action potential faster and speed up heart rate. This makes sense because it's that Phase 4 climb that really stalls cells when it comes to heart rate, particularly at the AV Node. Changing Phase 0 would help but not nearly as much as it changing Phase 0, it seems to me.

Now for the big one: why do beta blockers affect repolarization?

Do all beta blockers affect repolarization? Thought it was just sotalol ( k channel blockade)

 

[Ven0m]

Correct. It also doesn't affect phase 0 because those are L-type channels (which are acted on by non-dihydropyridine calcium channel blockers, type 4 antiarrhythmics)

Costanzo says that in addition to increasing the slope of nodal phase 4, sympathetic stimulation of nodal cells also increases nodal phase 0's slope by increasing inward Ca2+ current, which is what causes the increased conduction velocity.. what the

 

[JooceMan137]

Costanzo says that in addition to increasing the slope of nodal phase 4, sympathetic stimulation of nodal cells also increases nodal phase 0's slope by increasing inward Ca2+ current, which is what causes the increased conduction velocity.. what the

If I recall, I think it was because the cAMP-> Protein kinase A cascade from beta stimulation phosphorylates the calcium channel, making it more permeable.

 

[Ven0m]

If I recall, I think it was because the cAMP-> Protein kinase A cascade from beta stimulation phosphorylates the calcium channel, making it more permeable.

Yeah, you're right