title: Voltage-dependent modulation of L-type Ca2+ current by manidipine in guinea-pig heart cells.
abstract: Effects of manidipine, a dihydropyridine derivative, on L-type Ca2+ currents were examined in guinea-pig ventricular cells, using the whole-cell patch-clamp method. At a holding potential of -37 mV, manidipine decreased the Ca2+ current at concentrations above 0.1 nM, and abolished it at 100 nM (IC50 = 2.6 nM). At a holding potential of -78 mV, manidipine did not suppress the Ca2+ current at concentrations less than 100 nM, but increased the Ca2+ current slightly at a concentration of 10 nM. The antagonistic effect of manidipine was significant at concentrations above 100 nM (IC50 = 400 nM). The voltage-dependent effect of manidipine on the Ca2+ current may explain the weak negative inotropism of manidipine in ventricular muscles, and provide an electrophysiological basis for its vascular selectivity.
authors.affiliation: Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tohse
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Kanno
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009578:Nitrobenzenes; D010879:Piperazines
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine