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.
Matsuoka
T
T
Department of Physiology, Kobe University School of Medicine, Japan.
Nishizaki
T
T
Nomura
T
T
D000818:Animals; D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000098:blood supply; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D001464:Barium; C066425:efonidipine; D009529:Nicardipine; D002118:Calcium