Contractile Action of Mn2+ via Ca2+ Channels Activated by Bay K 8644 in Guinea-pig Taenia Coli

Mn²⁺ has been shown to inhibit K+-induced contraction of smooth-muscle, to induce contraction of smooth-muscle in Ca²⁺-free, K+ medium and to activate the contractile proteins of skinned fibres of smooth muscle cells. Further work has suggested that Mn²⁺ penetrates the cytoplasm through voltage-dependent Ca²⁺ channels when the cell membranes of smooth muscles are depolarized with K+. We have investigated whether in Ca²⁺-free medium, Mn²⁺ enters the cytoplasm through Ca²⁺ channels and induces contraction of guinea-pig taenia coli in the presence of Bay K 8644, a dihydropyridine Ca²⁺-channel agonist which prolongs the open state of the voltage-dependent Ca²⁺ channels in smooth-muscle cells. In Ca²⁺-free medium the application of 5 mM Mn²⁺ in the presence of Bay K 8644 caused contraction of and concomitant increase in Mn²⁺ uptake in guinea-pig taenia coli smooth muscle. In the presence of Bay K 8644 nifedipine, a dihydropyridine Ca²⁺ channel antagonist, dose-dependently inhibited both manganese uptake and the contraction induced by Mn²⁺. These results suggest that Mn²⁺ enters the cytoplasm through dihydropyridine-sensitive, voltage-dependent Ca²⁺ channels activated by Bay K 8644 and then induces contraction in taenia coli.