Effects of calcitonin gene-related peptide (CGRP) on Ca(2+)-channel current of isolated smooth muscle cells from rat vas deferens.
Effects of calcitonin gene-related peptide (CGRP), a putative non-adrenergic non-cholinergic neutrotransmitter on the electrical properties of the cell membrane, were investigated in enzymically dispersed smooth muscle cells from rat vas deferens. Under current clamp conditions, CGRP (up to 10(-7) M) did not induce significant changes in membrane potentials or input resistance in the resting state. The configurations of action potentials elicited by depolarizing current pulses were also unaffected, except that a prolongation of the duration of the action potentials by a high dose (10(-7) M) of CGRP was observed in some of the cells. Under whole cell voltage clamp conditions, the transient and sustained K+ currents, activated by depolarizing voltage-steps, were apparently decreased in the presence of 10(-9) to 10(-7) M CGRP. The peptide increased the voltage-gated Ca2+ current in cells loaded with 145 mM Cs+ solution in order to block the K+ currents. The voltage-dependency of the peak Ca2+ current was not changed by CGRP. Ba2+ (10.8 mM) was used as a charge carrier for the Ca(2+)-channel current to clarify further the effects of CGRP on the properties of the current. CGRP (10(-8) M) delayed the inactivation time course of the Ca(2+)-channel current and slowed the recovery from inactivation. The peptide did not affect the steady-state inactivation measured by changing the holding potential. The Ca(2+)-channel current in the presence of CGRP was suppressed by nicardipine (10(-6) M) to the same extent as the current under control conditions. The results suggest that CGRP modifies the L-type Ca2+ channel in smooth muscle cells.
Nakazawa
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Matsuki
N
N
D000818:Animals; D001464:Barium / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014649:Vas Deferens / Q000187:drug effects
D015220:Calcium Channels; D015221:Potassium Channels; D001464:Barium; D015740:Calcitonin Gene-Related Peptide