Article date: September 1991
By: J. Mironneau, S. Arnaudeau, C. Mironneau, in Volume 104, Issue 1, pages 65-70
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).
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 μm, respectively. In myometrium, the fenoverine concentration which blocked 50% of the slow Ca2+channel current (holding potential of −70 mV) was 2.3 μm.
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.
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.
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 afinity for inactivated Ca2+channels than for resting channels.
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).
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 μm, respectively. In myometrium, the fenoverine concentration which blocked 50% of the slow Ca2+channel current (holding potential of −70 mV) was 2.3 μm.
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.
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.
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 afinity for inactivated Ca2+channels than for resting channels.
DOI: 10.1111/j.1476-5381.1991.tb12386.x
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