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-depolymerization cycle, on Ba(2+) current (I(Ba)) flowing through voltage-gated Ca(2+) channels and carbachol (CCh)-induced sustained suppression of I(Ba) were examined in whole-cell voltage-clamped smooth muscle cells of guinea-pig ileum. 2 Colchicine (100 mu M) and vinblastine (100 mu M), microtubule depolymerizers. 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 concentration-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-dependent decrease in I(Ba) and the action of CCh on I(Ba). The inhibitory effects of 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 suppression of Ca(2+) channel activity, and that muscarinic sustained suppression of Ca(2+) channel current is mediated by a signal transduction element which involves microtubule cytoskeleton.