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Pacemaker action potential

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Lothric

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Hey,

FA mentions that ACh/adenosine decreases the rate of diastolic depolarization and reduce heart rate. When they write it like they do (ACh/adenosine) I get the impression that they mean that even adenosine causes a reduced heart rate. But that's not the case, right?

ACh binding to its receptor in this case causes activation of an inhibitory alpha-subunit in the G-protein, causing inactivation of adenylate cyclase and thus decreased amount of cAMP. So the less adenosine the less the heart rate is, with more Ach causing this greater lessening.

Or did I miss something?
 

Rahas

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Adenosine isn't a 2nd messenger, cAMP is. Both cardiac M2 and adenosine (A1) receptors act via Gi, and reduce cAMP. Adenosine has multiple cardiac effects via the A1R, thought I'm pretty sure this level of detail is unnecessary:
1.decreases If -> primary effect is bradycardia (SAN depression)
2.decreases Ca current -> primary effect is AVN depression (slowed conduction, increased refractory period; effect similar to verapamil on the AVN)
3.increases K conductance -> hyperpolarization
4.antagonizes sympathetic effects (which act via increasing cAMP)

But adenosine via A2 receptors on blood vessels -> vasodilation -> may cause reflex tachycardia. As far as I'm aware, tachycardia is actually a lot more common with adenosine than bradycardia.
 

Jabbed

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I feel like this is referring to the common use of adenosine as an antiarrhythmic. It opens potassium channels leading to hyperpolarization which produces a transient SA block.
 
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