IONIC BASIS OF THE ELECTROPHYSIOLOGICAL ACTIONS OF ADENOSINE CARDIOMYOCYTES

The purpose of this review is to examine the role of the extracellular A(1)-adenosine (Ado) receptor in modulating membrane potential and currents in cardiac cells. The cellular electrophysiological effects of adenosine are both cell type- and species-dependent, In supraventricular tissues (SA, AV node, and atrium) of all species studied, the ''direct'' cAMP-independent activation of the inwardly rectifying K+ current I-KAdo seems to be the most important action of adenosine. This current is activated bp both adenosine and acetylcholine and flows through K+ channels with unitary slope conductance of about 45 pS and an open time constant of 1.4 ms. The density of K+-ACh,Ado channels is much less in ventricular than in atrial myocytes, and thus adenosine has little or no effect on the ventricular action potential. In atrial myocytes adenosine has a small inhibitory effect on basal L-type calcium current (I-Ca,I-L), but no effect on T-type calcium current (I-Ca,I-T) In ventricular myocytes, adenosine does not inhibit I-Ca,I-L (except ferret), I-Ca,I-T, Or the sodium inward current I-Na. Adenosine has recently been shown to activate I-KATP in ventricular membrane patches, but the relevance of this finding remains to be defined. Irrespective of cell type and species, adenosine inhibits membrane currents that are stimulated by beta-adrenergic agonists and other agents known to stimulate the activity of the enzyme adenylyl cyclase. This indirect cAMP-dependent mechanism of action has been shown to be responsible for the inhibition by adenosine of isoproterenol-stimulated I-Ca,I-L, delayed rectifier K+ current (I-K), chloride current (I-Cl), the transient inward current I-Ti, and the pacemaker current I-F. The importance of the actions of adenosine on membrane currents in modulation of atrial, ventricular, sinoatrial, and atrioventricular nodal function are discussed. Likewise, the antiarrhythmic and proarrhythmic actions of adenosine are discussed and the clinical implications of these actions are noted.