MODULATION OF ATP-SENSITIVE K+ CHANNELS IN RABBIT VENTRICULAR MYOCYTES BY ADENOSINE A(1) RECEPTOR ACTIVATION

The objective of the present study was to characterize the role of ade nosine in the regulation of ATP-sensitive K+ (K-ATP) channel activity in isolated rabbit ventricular myocytes using the patch-clamp techniqu e. In an outside-out patch exposed to guanosine 5'-triphosphate and AT P at the intracellular surface, external adenosine stimulated K-ATP ch annel activity. In an inside-out patch exposed to external adenosine, ATP reduced K-ATP channel activity and guanosine 5'-triphosphate stimu lated K-ATP channel activity. Guanosine 5'-O-(3-thiotriphosphate) resu lted in a gradual increase of K-ATP channel activity even in the absen ce of adenosine. When myocytes were preincubated with pertussis toxin or 8-cyclopentyl-1,3-dipropylxanthine, adenosine A(1) receptor activat ion failed to activate the K-ATP channel. Analysis of the open and clo sed time distributions showed that adenosine A(1) receptor activation increased burst duration and decreased interburst duration. In a dose- response relationship for ATP, adenosine A(1) receptor activation shif ted the half-maximal inhibition of the K-ATP channel from 70 to 241 mu M.