CARDIOPROTECTIVE ACTIONS OF ATP-SENSITIVE K⁺ CHANNEL OPENERS (CROMAKALIM, PINACIDIL AND NICORANDIL) IN CARDIAC PURKINJE FIBERS

Abstract

Effects of ATP-dependent K⁺ channel openers on the action potentials and the contractile force in canine cardiac Purkinje fibers were examined. Cromakalim and pinacidil (0.3 to 10 μM), and nicorandil (0.3 to 1 mM) shortened both the 50% and 90% action potential durations (APD), and decreased the contractile force, in a concentration and frequency-dependent manner. These responses were reversible. The APD shortening and the negative inotropic effect induced by a switch of stimulation frequency (from 0.5 to 3 Hz) were potentiated by application of the openers. Other action potential parameters were unaffected, but the resting potential of relatively less negative voltage was hyperpolarized. These effects were potently antagonized by glibenclamide (a selective blocker of ATP-sensitive K⁺ channel). Under the calcium overload condition, the K⁺ channel openers abolished a delayed afterdepolarization and recovered the contractile force. These results suggest that the ATP-sensitive K⁺ channel openers increase the K⁺ conductance and simultaneously may possess cardioprotective actions to reduce the cellular Ca²⁺ level in calcium overloaded cells.