[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⁺-Ca²⁺ 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.