The voltage-dependent non-selective cation channel sensitive to the L-type calcium channel blocker efonidipine regulates Ca2+ influx in brain vascular smooth muscle cells.

The present study investigated the ion channel responsible Ca2+ influx in cultured smooth muscle cells from bovine brain arteries by monitoring Ba2+ currents. Voltage pulses at a range between -100 and +100 mV from a holding potential of 0 mV induced currents and the current/voltage (I/V) relations were linear with a reversal potential of +/- 0 mV. The currents were increased by elevating extracellular Ba2+ concentrations, suggesting that the voltage-sensitive non-selective cation channel, which favors Ca2+ influx, is expressed in brain vascular smooth muscle cells. In contrast, when voltage pulses at a range between -50 to +50 mV from a holding potential of -80 mV were applied to carotid smooth muscle cells, inward currents were evoked by depolarization to > or = -10 mV and the I/V relations were bell-shaped, typical for the L-type calcium channels. The dihydropyridine derivatives, efonidipine and nicardipine, inhibited the L-type Ca2+ channel-operated currents in carotid smooth muscles, and further efonidipine had an inhibitory effect also on non-selective cation currents in brain vascular smooth muscle cells. These results suggest that the voltage-dependent non-selective cation channel expressed in brain vascular smooth muscle cells is sensitive to a kind of the dihydropyridine derivatives and regulates Ca2+ influx.