Actions of adenosine on the sinus node.

Adenosine has a negative chronotropic effect on pacemaker tissue. This is a direct effect on pacemaker cells and is mediated by extracellular adenosine receptors (i.e., A1 subtype). Adenosine also produces a shift in pacemaker site. There is a hierarchy in sensitivity of pacemakers to adenosine with the lower, i.e., His bundle, pacemaker being most sensitive. The pacemaker slowing caused by adenosine is due to a hyperpolarization of the membrane which results in a decrease in phase 4 depolarization. The hyperpolarization is presumably the result of an adenosine-activated K+ conductance. Adenosine and acetylcholine have similar effects, being additive up to a maximal response, and may be the result of activation of the same K+ channels via different receptors. Adenosine may be important in modulating several bradyarrhythmias seen clinically. Future studies will help to determine more precisely the mechanism of action of adenosine at the molecular level as well as the involvement of adenosine in pacemaker function during normal and abnormal conditions.