Skeletal muscle L-type current is blocked by nonspecific cation channel antagonists. Acute block of L-type currents evoked by step depolarizations to +30 mV by 100 μM Gd3+ (A), 100 μM La3+ (B), 100 μM 2-APB (C), and 20 μM SKF 96356 (D). The test pulse was applied after a prepulse protocol (see Materials and methods) (Adams et al., 1990). Results of these experiments and application of DMSO vehicle (0.01%) control experiments are summarized in E. For trivalent cations, maximal block was generally achieved in <30 s after gravity perfusion of the 30-mm dish, whereas longer perfusion times were required for maximal block by 2-APB (1–2 min) and SKF 96356 (2–3 min). The asterisk indicates a significant difference for current (measured at the end of a 200-ms test pulse) remaining in myotubes exposed to blockers relative to DMSO-treated control cells (P < 0.0001, ANOVA). Although not indicated, block by SKF 96356 measured at the end of a 500-ms test pulse was also significantly (P < 0.00008, t test) different than DMSO controls. Throughout, the error bars represent ± SEM.
