Fenoverine inhibition of calcium channel currents in single smooth muscle cells from rat portal vein and myometrium.
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.
Mironneau
J
J
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, Université de Bordeaux II, France.
Arnaudeau
S
S
Mironneau
C
C
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
D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D010640:Phenothiazines; C048314:fenoverine; D010879:Piperazines