Skinned coronary smooth muscle: Calmodulin, calcium antagonists, and cAMP influence contractility

Abstract

The effects of Ca²⁺, calmodulin, cAMP, the catalytic subunit of cAMP-dependent protein kinase (CSU) and some Ca²⁺ antagonists were studied in chemically (Triton X-100) skinned coronary smooth muscle. Calmodulin increased the Ca²⁺ responsiveness of the muscle fiber as indicated by the reduction in the threshold as well as the half-maximal activating Ca²⁺ concentration. Trifluoroperazine, a calmodulin antagonist, inhibited Ca²⁺-calmodulin-induced contraction. Both cAMP anCSU were effective inhibitors of contraction induced at an intermediate Ca²⁺ concentration. Fendiline, a Ca²⁺-antagonist, at 2×10⁻⁴ M produced a significant inhibitory effect, which was reduced by increasing the Ca²⁺ concentration. From other Ca²⁺ antagonists tested, W-7, but not D600 and verapamil, produced some inhibitory effect. The data indicate that the responses of skinned coronary smooth muscle to Ca²⁺, calmodulin and cAMP are similar to those obtained with other skinned smooth muscles. Furthermore, skinned fiber preparation can serve as a useful tool to investigate possible direct effects of drugs on the activating and regulatory systems in smooth muscle.