The antifungal antibiotic clotrimazole potently inhibits L-type calcium current in guinea-pig ventricular myocytes

The antimycotic agent clotrimazole (CLT) is a promising potential therapeutic agent for a variety of diseases including cancer. Although it is known that CLT alters calcium homeostasis in many cell types, its cardiac effects are virtually unknown. We investigated the effects of CLT on L-type calcium current (I-Ca,I-L) and action potentials in guinea-pig ventricular myocytes. CLT (5, 25 and 50 mu M) inhibited basal I-Ca,I-L by 16, 59 and 93%, respectively. The inhibitory effect of CLT was rapid and the peak effect was attained within 3 min. At a concentration of 25 mu M, the inhibitory effect of CLT was partially reversible whereas the response to 50 mu M CLT persisted following drug withdrawal. CLT abbreviated action potential duration at 50 and 90% of repolarization and suppressed the plateau significantly. These results indicate that CLT may have important cardiac effects at concentrations used to induce the antiproliferative action of the drug.