Adenosine mechanism of action

[studylol]

Hello friends,

I'm having difficulty understanding the MoA of adenosine as an antiarrhythmic agent. I understand that its immediate affect is to elevate K+ efflux from cells. How does this lead to a change in calcium current current as FA states?

Thanks!

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[tn4596]

At the beginning of phase 4 you have Na influx and K efflux slowly depolarize the cell till membrane potential reach -50, then the T type Ca channel open and the Ca influx create further depolarization. Since adenosine facilitate K influx, it will prolong the time it take for the membrane to reach -50, therefore prolong Ca influx and phase 4.

 

[stop2stop]

At the beginning of phase 4 you have Na influx and K efflux slowly depolarize the cell till membrane potential reach -50, then the T type Ca channel open and the Ca influx create further depolarization. Since adenosine facilitate K influx, it will prolong the time it take for the membrane to reach -50, therefore prolong Ca influx and phase 4.

Is there anyway you (Or someone else) could elaborate on this? Did you mean to say that adenosine cause K efflux, thus hyperpolarizing the cell? That would make sense to me here, but K influx not as much.

 

[worldbeater]

Is there anyway you (Or someone else) could elaborate on this? Did you mean to say that adenosine cause K efflux, thus hyperpolarizing the cell? That would make sense to me here, but K influx not as much.

This is right, potassium efflux causes hyperpolarizing (causing the cell to be more negative). Adenosine is used in a condition with a fast heart rate like SVT, so this MOA makes sense.

 

[stop2stop]

This is right, potassium efflux causes hyperpolarizing (causing the cell to be more negative). Adenosine is used in a condition with a fast heart rate like SVT, so this MOA makes sense.

Thanks for the reply, makes sense to me as well. I did notice something about adenosine having an effect on inward rectifying currents though. Perhaps that is what the earlier poster was referring to?

 

[StilgarMD]

The depolarization of the SA node relies on the funny current. The Funny channels are not singly-permeable channels - they are permeable to both K and Na (sometimes channels like these get called "Non-selective cation channels"). This is why the channel doesn't produce the kind of strong depol a pure sodium channel would produce or the hyperpolarization a pure K channel would produce - it produces a depolarization of intermediate slope, and since it is still a depolarization, you know its more permeable to Na than K. (Wiki link)

Adenosine binds to A1 receptors, which are coupled to Gi and less cAMP. Less cAMP diminishes funny channel activity leading to an even flatter slow. It's activity also opens up more pure K+ channels (the ones that establish the RMP), which lead to a lower start point. These two combine to make Adenosine a negative chronotrope.

Adenosine acting on the AV node through the same receptor leads to less L-type calcium channel activity, and negative dromotrope effects.

Source: http://www.cvpharmacology.com/antiarrhy/adenosine

 

[stop2stop]

The depolarization of the SA node relies on the funny current. The Funny channels are not singly-permeable channels - they are permeable to both K and Na (sometimes channels like these get called "Non-selective cation channels"). This is why the channel doesn't produce the kind of strong depol a pure sodium channel would produce or the hyperpolarization a pure K channel would produce - it produces a depolarization of intermediate slope, and since it is still a depolarization, you know its more permeable to Na than K. (Wiki link)

Adenosine binds to A1 receptors, which are coupled to Gi and less cAMP. Less cAMP diminishes funny channel activity leading to an even flatter slow. It's activity also opens up more pure K+ channels (the ones that establish the RMP), which lead to a lower start point. These two combine to make Adenosine a negative chronotrope.

Adenosine acting on the AV node through the same receptor leads to less L-type calcium channel activity, and negative dromotrope effects.

Source: http://www.cvpharmacology.com/antiarrhy/adenosine

Thanks! So it would be the K efflux channels (RMP channels) that primary work with adenosine and not due to K influx? Thanks again for your time.

 

[StilgarMD]

Thanks! So it would be the K efflux channels (RMP channels) that primary work with adenosine and not due to K influx? Thanks again for your time.

K Influx can only take place through an ATPase (like the Na-K ATPase) since that is moving potassium up it's electrochemical gradient. If you hear "channel", remember it is facilitating diffusion down the gradient, which in this case means K efflux. Most membranes are highly permeable to K as is, which is why the RMP is pretty close to K+'s equilibrium potential. Tuning membrane permeability is what allows you to change the direction and rate at which the membrane potential changes.