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Inhibitory effects of cilnidipine on peripheral and brain N-type Ca2+ channels expressed in BHK cells
Kenichi Kato1, Minoru Wakamori, Yasuo Mori
1Department of Cell Physiology and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, Japan. kenkato@college.fdcnet.ac.jp
Abstract:
We investigated differences in electrophysiological characteristics between peripheral and central N-type Ca(2+) channels, containing alpha(1B-a) and a(1B-c), respectively. In addition, we examined the inhibitory effects of cilnidipine, a dihydropyridine (DHP) derivative, on both channels. Both alpha(1B) subunits were transiently expressed in BHK cells, and then analyzed using the whole-cell patch-clamp technique. The current-voltage relationship showed that alpha(1B-c) currents were activated at more negative potentials than alpha(1B-a) currents. The voltage-dependent steady-state inactivation and activation showed that the V(1/2) values for inactivation and activation of alpha(1B-c) (-88.5+/-1.3 and -33.2+/-1.3 mV) were both significantly more negative than those for alpha(1B-a) (-83.3+/-1.3 and -27.9+/-2.3 mV). Despite the different electrophysiological characteristics of these two N-type channels, cilnidipine blocked both with similar potency within the range 0.1 to 10 microM. Furthermore, cilnidipine had no effect on the I-V relationships or the steady-state inactivation curves. Our data indicate that the spliced positions of alpha(1B-a) and a(1B-c) may affect not only their voltage-sensing abilities but also the kinetics of channel activation and inactivation. The data also suggest that cilnidipine binds to sites independent of those controlling voltage-sensing and channel kinetics in these alpha(1B) subunits.
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