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

1 Effects of agents, which affect microtubule polymerization-depolymerizati on cycle, on Ba2+ current (I-Ba) flowing through voltage-gated Ca2+ channel s and carbachol (CCh)-induced sustained suppression of I-Ba were examined i n whole-cell voltage-clamped smooth muscle cells of guinea-pig ileum. 2 Colchicine (100 mu M) and vinblastine (100 mu M), microtubule depolymeriz ers. increased the ampitude of I-Ba. Lumicolchicine (100 mu M), an inactive analogue of colchicine, had no effect on I-Ba. 3 Taxol (1-100 mu M), a microtubule polymerizer, decreased I-Ba in a concen tration-dependent manner and accelerated the rate of inactivation of I-Ba. Baccatin III (100 mu M), an inactive analogue of taxol, had no effect on I- Ba. 4 Colchicine (100 mu M) and vinblastine (100 mu M), but not lumicolchicine (100 mu M), decreased or abolished the sustained component of CCh (10 mu M) -induced I-Ba suppression. 5 Pretreatment with taxol (10-100 mu M) resulted in a concentration-depende nt decrease in I-Ba and the action of CCh on I-Ba. The inhibitory effects o f taxol and CCh on I-Ba were not additive. 6 Colchicine (100 mu M) or taxol (100 mu M) had no effect on voltage-gated K+ channel current or CCh-induced non-selective cationic channel current. 7 These results suggest that polymerization of microtubules leads to suppre ssion of Ca2+ channel activity, and that muscarinic sustained suppression o f Ca2+ channel current is mediated by a signal transduction element which i nvolves microtubule cytoskeleton.