Effects of R56865 on membrane currents in isolated ventricular cardiomyocytes of the guinea-pig

In isolated heart muscle, the compound R56865 (N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazolamine) has been shown to protect against intoxication by cardiac glycosides. We studied the influence of R56865 on various membrane currents in single isolated ventricular cardiomyocytes of the guinea-pig. The sodium current, I Na, was investigated at reduced extracellular Na + (30 mM) in the presence of Cd 2+ to block the calcium current, I Ca, and with Cs + substituted for K + to reduce the K + currents, I K. Under these conditions, R56865 concentration dependently decreased the peak I Na with a half-maximum effect at about 1 μM. The steady state inactivation and normalized conductance of I Na were not significantly different from the control. In ‘normal’ Tyrode solution, R56865 (10 μM) did not markedly reduce I Ca, and did not affect the quasi steady state I K, which was taken as an index of K + conductance. We conclude that R56865 possesses Na + channel-blocking properties, whereas I Ca and membrane K + conductance were not influenced.