Block and activation of the hyperpolarization-activated inward current by Ba and Cs in frog sinus venosus

Voltage clamp experiments were performed on isolated frog sinus venosus trabeculae using the double mannitol gap voltage clamp technique. On hyperpolarization from the holding potential (-30, -50 mV) to various potential levels slow activation of inward current was recorded. Several basic features of this current system resemble those of the current if in mammalian pace-maker tissues. The current activates from a threshold ranging between -50, -70 mV and increases in the inward direction with the negative pulse amplitude. Conductance measurements during current development show a conductance increase. The current is strongly reduced during perfusion with Na-free medium. However, there were several important differences in its properties from those of the if current in other preparations. Ba in concentrations of 0.3-5 mM reduces the amplitude of the inward current in a concentration-dependent manner. Cs in low concentration range (1-10 mM) fails to have any effect on the time dependent current. Cs concentrations higher than 10 mM increase the current amplitude in a dose-dependent manner. The current increase induced by Cs still remains in Na-free solution and is not affected by Cl replacement. These results suggest that Cs may carry inward current. The identity of the ionic mechanism responsible for the observed current is discussed.