Blockade by calmodulin inhibitors of Ca2+ channels in smooth muscle from rat vas deferens

Article date: May 1993

By: Ken Nakazawa, Katsuya Higo, Kazuho Abe, Yoshio Tanaka, Hiroshi Saito, Norio Matsuki, in Volume 109, Issue 1, pages 137-141

Effects of three compounds which are used as calmodulin inhibitors (trifluoperazine, W‐7 and calmidazolium) on Ca2+ channels were investigated in smooth muscle from rat vas deferens.

All three calmodulin inhibitors relaxed the smooth muscle precontracted by a high concentration of KCl (63.7 mm). The order of potency for the relaxation was trifluoperazine > W‐7 > calmidazolium.

In binding studies using a microsomal fraction of vas deferens, all these calmodulin inhibitors displaced specific [3H]‐nimodipine binding. Trifluoperazine and W‐7 inhibited the binding at concentrations that relaxed the smooth muscle whereas calmidazolium inhibited at concentrations much lower than those necessary for muscle relaxation.

Ba2+ current flowing through voltage‐gated Ca2+ channels was measured under whole‐cell voltage‐clamp conditions in isolated smooth muscle cells. The Ba2+ current was suppressed by the three calmodulin inhibitors in the concentration‐range where inhibition of [3H]‐nimodipine binding was observed. Neither voltage‐dependence nor the inactivation time course of Ba2+ current were affected by these compounds.

The results suggest that the calmodulin inhibitors directly block Ca2+ channels in the smooth muscle cells. The channel inhibition by trifluoperazine and W‐7, but perhaps not that by calmidazolium, may be responsible for the muscle relaxation observed with these compounds.

Effects of three compounds which are used as calmodulin inhibitors (trifluoperazine, W‐7 and calmidazolium) on Ca2+ channels were investigated in smooth muscle from rat vas deferens.

All three calmodulin inhibitors relaxed the smooth muscle precontracted by a high concentration of KCl (63.7 mm). The order of potency for the relaxation was trifluoperazine > W‐7 > calmidazolium.

In binding studies using a microsomal fraction of vas deferens, all these calmodulin inhibitors displaced specific [3H]‐nimodipine binding. Trifluoperazine and W‐7 inhibited the binding at concentrations that relaxed the smooth muscle whereas calmidazolium inhibited at concentrations much lower than those necessary for muscle relaxation.

Ba2+ current flowing through voltage‐gated Ca2+ channels was measured under whole‐cell voltage‐clamp conditions in isolated smooth muscle cells. The Ba2+ current was suppressed by the three calmodulin inhibitors in the concentration‐range where inhibition of [3H]‐nimodipine binding was observed. Neither voltage‐dependence nor the inactivation time course of Ba2+ current were affected by these compounds.

The results suggest that the calmodulin inhibitors directly block Ca2+ channels in the smooth muscle cells. The channel inhibition by trifluoperazine and W‐7, but perhaps not that by calmidazolium, may be responsible for the muscle relaxation observed with these compounds.

DOI: 10.1111/j.1476-5381.1993.tb13543.x

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