Modulation of voltage-dependent facilitation of the T-type calcium currentby sodium ion in isolated frog atrial cells

Sodium ions have been reported to alter the permeation properties of L- and N-type Ca2+ channels. Here in frog atrial cardiomyocytes under whole-cell patch-clamp conditions, we have examined the effects of lowering the extern al Na+ concentration on the amplitude of T-type Ca2+ current, I-CaT, and on the relief of its steady-state inactivation by large depolarizing prepulse s, I-CaT facilitation. A partial reduction in Na+ ion concentration did not significantly alter I-CaT amplitude elicited at -50 mV. However, after a l arge depolarization, low-Na+ solutions enhanced the relief of inactivation and induced I-CaT facilitation. This facilitation occurred independently of the divalent charge carrier, high intracellular Ca2+ buffering or the intr acellular Na+ content. Its effects were additional to the beta -adrenergic effects mediated by a decrease of G(i/o)-protein inhibitory tone. In Ca2+-f ree solution the very large T-type current, then carried by Na+ ions, showe d only a weak relief of inactivation. In conclusion, I-CaT facilitation - w hich, as previously reported, is modulated by the transient voltage-depende nt relief of G(i)-protein inhibitory tone - is further enhanced in a low-Na + solution. In Ca2+-free solution, relief of inactivation due to re-opening s dependent on the divalent charge carrier is improbable. It thus appears t hat for a short while after a large depolarization, external Na+ compete wi th Ca2+ ions on permeation-controlling sites, so as to modulate channel re- openings and thus the amplitude of voltage-facilitated I-CaT independently of the control exerted by the inhibitory G-protein.