title: Fenoverine inhibition of calcium channel currents in single smooth muscle cells from rat portal vein and myometrium.
abstract: 1. The effects of fenoverine, an antispasmodic drug, have been studied on the Ca2+ channel currents of isolated cells from rat portal vein and pregnant myometrium by the patch-clamp technique (whole-cell configuration). 2. Fenoverine inhibited both fast and slow Ca2+ channel currents in a concentration-dependent manner. Half-inhibition of fast Ca2+ channel current (holding potential of -70 mV) and slow Ca2+ channel current (holding potential of -40 mV) in portal vein smooth muscle were obtained at concentrations of 7.5 and 1.9 microM, respectively. In myometrium, the fenoverine concentration which blocked 50% of the slow Ca2+ channel current (holding potential of -70 mV) was 2.3 microM. 3. Administration of fenoverine at rest reduced both Ca2+ channel currents. Currents activated repetitively, at a rate between 0.05 and 0.1 Hz, were inhibited equally which indicates an absence of use-dependent inhibition. 4. When cells held at depolarized membrane potentials at which fast or slow Ca2+ channel currents were strongly inactivated, the inhibitory effects of fenoverine were enhanced on both Ca2+ channel currents which indicates that the fenoverine-induced inhibition was voltage-dependent. The fenoverine concentrations which blocked the inactivated Ca2+ channels were 5-7 times lower than those which blocked the resting Ca2+ channels. 5. Our results show that fenoverine depresses inward currents through fast and slow Ca2+ channels. This effect may be explained by the preferential binding of fenoverine to resting Ca2+ channels. In addition, fenoverine has a higher affinity for inactivated Ca2+ channels than for resting channels.
authors.affiliation: Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, Université de Bordeaux II, France.
authors.forename: J
authors.initials: J
authors.lastname: Mironneau
authors.forename: S
authors.initials: S
authors.lastname: Arnaudeau
authors.forename: C
authors.initials: C
authors.lastname: Mironneau
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009215:Myometrium / Q000166:cytology / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010640:Phenothiazines / Q000494:pharmacology*; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects; D010879:Piperazines
chemical_list: D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D010640:Phenothiazines; C048314:fenoverine; D010879:Piperazines