Comparison of Purinergic and Cholinergic Receptor-Mediated Effects on Action Potential in Rat Atrium

Cho, Bek Hyun; Kwak, Seung Ho; Kim, Dae Young; Lee, Sam Yong

Abstract

In the heart, it has been known that acetylcholine and adenosine produce similar negative inotropic effects protecting myocardial tissues from some overloaded states. However, the precise mechanism underlying the similarities of action by both agents is yet to be difined. The present study was, therefore, undertaken to investigate the characteristics of cholinergic and purinergic actions by observing the influences of some antagonists and channel blockers on the effects of both agents in the variables of action potentials (AP) of rat atria. Acetycholine hyperpolarized the membrane potential (2x10-5muM), increased the rate of phase 0 depolarization (10-6 and 5x10-6muM) and shortened AP duration dose-dependently (2x10-7~10-5muM). However, the only significant effects of adenosine were a dose-dependent shortening of AP duration at the doses greater than 10-5muM, and the Magnitude of AP-shortening effects by adenosine were lesser than those by acetylcholine. The rank order of increasing potency for AP-shorting effects of some cholinergic and purinergic agonists was CPA> carbachol> acetylcholine> adenosine. Atropine (10-6muM), cholinergic antagonist, attenuated the AP-shortening effects of acetylcholine (5x10-6muM) and of carbachol (10-6muM), but did not affect those of adenosine (10-4muM), and of CPA (10-6muM). On the contary, DPCPX (2x10-6muM), purinergic antagonist, attenuated the AP-shortening effects of adenosine and of CPA, but did not affect those of acetylcholine and of carbachol. 4-Aminophridine (5x10-4muM) and tetraethylammonium (10-3muM), potassium channel blockers, significantly inhibited the AP-shortening effects of the four agents. From these results, it is inferred that acetylcholine or adenosine binds to different membrane receptors (muscarinic acetylpcholine receptors of P1-purinergic receptors) linked with a potassium channel via a common pathway, and thus, the similarities between the AP-shortening effects of acetylcholine and adenosine were from the fact that both substances activate the same channel population.