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Fenoverine inhibition of calcium channel currents in single smooth muscle cells from rat portal vein and myometrium
Author(s) -
Mironneau J.,
Arnaudeau S.,
Mironneau C.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12386.x
Subject(s) - myometrium , biophysics , chemistry , membrane potential , patch clamp , reversal potential , channel blocker , calcium , electrophysiology , endocrinology , medicine , anatomy , biology , biochemistry , receptor , uterus , organic chemistry
1 The effects of fenoverine, an antispasmodic drug, have been studied on the Ca 2+ 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 Ca 2+ channel currents in a concentration‐dependent manner. Half‐inhibition of fast Ca 2+ channel current (holding potential of −70 mV) and slow Ca 2+ channel current (holding potential of −40 mV) in portal vein smooth muscle were obtained at concentrations of 7.5 and 1.9 μ m , respectively. In myometrium, the fenoverine concentration which blocked 50% of the slow Ca 2+ channel current (holding potential of −70 mV) was 2.3 μ m . 3 Administration of fenoverine at rest reduced both Ca 2+ 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 Ca 2+ channel currents were strongly inactivated, the inhibitory effects of fenoverine were enhanced on both Ca 2+ channel currents which indicates that the fenoverine‐induced inhibition was voltage‐dependent. The fenoverine concentrations which blocked the inactivated Ca 2+ channels were 5–7 times lower than those which blocked the resting Ca 2+ channels. 5 Our results show that fenoverine depresses inward currents through fast and slow Ca 2+ channels. This effect may be explained by the preferential binding of fenoverine to resting Ca 2+ channels. In addition, fenoverine has a higher afinity for inactivated Ca 2+ channels than for resting channels.