Antagonism by adenosine and ATP of an isoprenaline-induced background current in guinea-pig ventricular myocytes

Abstract

A background current induced by isoprenaline, and its modulation by adenosine and ATP, have been studied using the whole cell patch clamp technique in guinea-pig ventricular myocytes. Isoprenaline (1-2000 nM) caused an inward shift of the holding current, in addition to increasing the inward calcium current (ICa). The effect on the background current was maximal earlier than the increase in ICa, but was of shorter duration. The magnitude of the background current was concentration dependent with a EC50 of 8 nM. This current was unaffected by tetrodotoxin 20 microM, Cd 200 microM or verapamil, 10 microM and potassium channel blockade (intracellular Cs, extracellular Cs 20 mM, Ba 2 mM or tetraethylammonium 10 mM). Lowering the chloride content of the electrode solution reduced the magnitude of the background current. The background current was also induced by histamine (1 or 10 microM). Adenosine (10-1000 microM) and and ATP (200 microM) antagonised the isoprenaline induced background current and the increase in ICa. The histamine effects on these currents were also reduced by adenosine. These results suggest that this background current may be carried by chloride ions and may be mediated via an increase in intracellular cyclic AMP concentration. Antagonism of this current may contribute to the antiarrhythmic actions of adenosine and ATP but their mechanisms of action are yet to be determined.