sensitizer, in guinea pig atrial cells

Ž . 2q Objective: To define the electrophysiologic mechanism s by which MCI-154, a putative Ca sensitizer, produces a positive inotropic response without a positive chronotropic response, we examined effects of MCI-154 on the action potential of atrial preparations and the membrane currents of atrial myocytes. Methods: The action potentias were recorded from left atrial and sinoatrial node preparations of guinea pigs by the use of standard microelectrode techniques. The whole-cell membrane currents were recorded from enzymatically-dissociated guinea pig atrial myocytes using conventional patch clamp techniques. Results: In isolated left atria, MCI-154 increased the developed tension in a concentration-dependent manner. MCI-154 at concentrations of 10 and 100 mM increased the action Ž . potential duration APD in left atria stimulated at 0.5 Hz. In sinoatrial node preparations MCI-154 at a concentration of 100 mM produced a negative chronotropic response and prolonged APD. In single right atrial myocytes, MCI-154 at concentrations of 10 and 100 2q q Ž . mM failed to increase the inward L-type Ca current, but decreased the delayed rectifier K current I in a concentration-dependent K manner. MCI-154 decreased I elicited by short depolarizing pulses more markedly than that induced by long depolarizing pulses. In K addition, MCI-154 produced only a little inhibition of I in the presence of E-4031, a specific blocker of rapidly activating component of K Ž . I I . Conclusions: MCI-154 preferentially blocks I and the inhibitory action on I may be partly involved in the negative K Kr Kr Kr chronotropic and positive inotropic responses in atrial preparations. q 1998 Elsevier Science B.V. All rights reserved.