Characteristics of the second inward current in cells isolated from rat ventricular muscle

The second inward current (Isi) in single cells isolated from ventricular muscle of adult rat hearts was measured in response to step depolarizations under voltage-clamp conditions. The major ion carrying this current was Ca, and Isi was reduced or abolished by Mn, Ni, Cd, nifedipine, nimodipine and D600. Sr and B could substitute for Ca as charge carriers, and reduced the rate of apparent inactivation of Isi. These effects of Sr and Ba, together with the relation between the steady level of apparent inactivation and membrane potential in Ca containing solution, were taken as evidence that inactivation was at least in part dependent on internal Ca. The reduction of external Na to 11% of normal caused a reduction in peak Isi when Ca was present in the external solution, but did not reduce Isi when Ca was replaced by Sr. It therefore seems unlikely that Na is a major charge carrier for Isi under the conditions of our experiments. The time-to-peak and rate of apparent inactivation of Isi were faster than in previous studies that used multicellular preparations. Both the kinetics and peak amplitude of Isi were markedly dependent on temperature (Q10 close to 3). Contraction of the cells, which was monitored optically, was initiated within 3 ms of the peak Isi, reached a maximum level after approximately 40-50 ms, and was about 100 ms in duration.