HYDROGEN PEROXIDE-INDUCED STIMULATION OF L-TYPE CALCIUM CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES AND ITS INHIBITION BY ADENOSINE AL RECEPTOR ACTIVATION

Hydrogen peroxide (H2O2) produces complex cardiac effects that may inv olve altered calcium homeostasis. The cardiotoxic effects of H2O2 can be attenuated by adenosine Al receptor agonists. The present study exa mined the effect of H2O2 on L-type Ca++ current (I-Ca,I-L) in guinea p ig ventricular myocytes under two different recording conditions and t he influence of adenosine receptor agonists. H2O2 (100 mu M), did not have any significant effect on I-Ca,I-L, under conventional whole cell patch configuration. However, when recorded under nystatin perforated patch configuration, H2O2 caused a gradual and significant increase ( 84 +/- 14%) in I-Ca,I-L compared to control values. N-6-cyclopentylade nosine (CPA), an adenosine Al receptor agonist, significantly attenuat ed the effect of H2O2. The inhibitory effect of N-6-cyclopentyladenosi ne was antagonized by 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor antagonist. The A2A and A3 receptor agonists, 2-p-(2-Carb oxyethyl)phenethylamino-5'- N- ethylcarboxamidoadenosine (CGS-21680) a nd -9H-purin-9-yl]-N-methyl-beta-D-ribofuranuronamide , respectively, did not modulate the enhancement of I-Ca,I-L by H2O2. Moreover the eff ects of N-6-cyclopentyladenosine were mimicked by the protein kinase C inhibitor bisindolylmaleimide. Thus, our results demonstrate a potent stimulatory effect of H2O2 on I-Ca,I-L in guinea pig ventricular myoc ytes. We further demonstrate that adenosine A1 receptor activation att enuates this effect. Our results suggest a potential basis for altered calcium homeostasis in response to H2O2 as well as the salutary effec ts of Al receptor activation against H2O2-induced cardiotoxicity.