Microtubule cytoskeleton involvement in muscarinic suppression of voltage‐gated calcium channel current in guinea‐pig ileal smooth muscle

• Published in: British journal of pharmacology 1999-08, Vol.127 (7), p.1703-1711
• Main Authors: Unno, T, Komori, S, Ohashi, H
• Format: Article
• Language: English
• Subjects: Animals; barium; Barium - pharmacology; Biological and medical sciences; Ca2+ channel current; Calcium Channels - drug effects; Calcium Channels - physiology; Calcium Channels, N-Type; Carbachol; Carbachol - pharmacology; Cell Membrane - drug effects; Cholinergic system; colchicine; Colchicine - pharmacology; Cytochalasin B - pharmacology; Cytoskeleton - drug effects; Guinea Pigs; guinea‐pig ileum; Ileum - drug effects; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; microtubule cytoskeleton; Microtubules - drug effects; Muscarinic Agonists - pharmacology; Muscle, Smooth - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Paclitaxel - pharmacology; Patch-Clamp Techniques; Phalloidine - pharmacology; Pharmacology. Drug treatments; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; smooth muscle; taxol; Vinblastine - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0702711

Effects of agents, which affect microtubule polymerization‐depolymerization cycle, on Ba2+ current (IBa) flowing through voltage‐gated Ca2+ channels and carbachol (CCh)‐induced sustained suppression of IBa were examined in whole‐cell voltage‐clamped smooth muscle cells of guinea‐pig ileum. Colchicine (100 μM) and vinblastine (100 μM), microtubule depolymerizers, increased the ampitude of IBa. Lumicolchicine (100 μM), an inactive analogue of colchicine, had no effect on IBa. Taxol (1–100 μM), a microtubule polymerizer, decreased IBa in a concentration‐dependent manner and accelerated the rate of inactivation of IBa. Baccatin III (100 μM), an inactive analogue of taxol, had no effect on IBa. Colchicine (100 μM) and vinblastine (100 μM), but not lumicolchicine (100 μM), decreased or abolished the sustained component of CCh (10 μM)‐induced IBa suppression. Pretreatment with taxol (10–100 μM) resulted in a concentration‐dependent decrease in IBa and the action of CCh on IBa. The inhibitory effects of taxol and CCh on IBa were not additive. Colchicine (100 μM) or taxol (100 μM) had no effect on voltage‐gated K+ channel current or CCh‐induced non‐selective cationic channel current. These results suggest that polymerization of microtubules leads to suppression of Ca2+ channel activity, and that muscarinic sustained suppression of Ca2+ channel current is mediated by a signal transduction element which involves microtubule cytoskeleton. British Journal of Pharmacology (1999) 127, 1703–1711; doi:10.1038/sj.bjp.0702711