[Electrophysiological Effects of Ionophore-induced Increases in Intracellular Na + in Cardiomyocytes].

Na ionophores increase intracellular Na ⁺ ([Na ⁺ ]i). Membrane potentials and currents were measured using microelectrode and whole-cell patch-clamp techniques. Monensin (10 ^-6 -3×10 ^-5 M) reduced the slope of the pacemaker potentials and shortened the action potential duration (APD) in sino-atrial nodal and Purkinje cells. Monensin (10 ^-5 M) shortened the APD and reduced the amplitude of the plateau phase in ventricular myocytes. Monensin decreased the hyperpolarization-activated inward current (I _f ), and it increased the transient outward potassium current (I _to ) in Purkinje cells. In addition, monensin decreased the sodium current (I _Na ), shifting the inactivation curve to the hyperpolarized direction. Moreover, monensin decreased the L-type calcium current (I _Ca ) in ventricular myocytes. The Na ⁺ -Ca ²⁺ exchange current (I _Na-Ca ) was augmented particularly in the reverse mode, and the Na ⁺ -K ⁺ pump current (I _Na-K ) was also activated by monensin in cardiomyocytes. The ATP-activated potassium current (I _K,ATP ) could be induced by monensin. Notably, the inward rectifying K ⁺ current (I _K1 ), and the slow delayed outward K ⁺ current (I _Ks ) were not affected evidently by monensin. Collectively, alteration of [Na ⁺ ]i can influence the activities of various ion channels and transporters. Thus, the significance of altered [Na ⁺ ]i should be taken into consideration in the action of drugs affecting [Na ⁺ ]i such as digitalis, Na ⁺ channel blockers, and Na ⁺ channel activating agents.