Relaxation of skinned coronary arteries depends on the relative concentrations of Ca2+, calmodulin and active cAMP-dependent protein kinase

Abstract

Maximally contracted detergent skinned coronary smooth muscle fibres are relaxed by lowering the concentration of free Ca2+. The extent and rate of relaxation depends on the concentration of free Ca2+ and calmodulin (CaM) suggesting that it is the Ca2+ X CaM complex which is responsible for maintaining tension. At a fixed concentration of Ca2+ and CaM further relaxation can be achieved by addition of the catalytic subunit of the cAMP-dependent protein kinase (cAMP-kinase). The extent as well as the relaxation rate depend on the concentration of cAMP-kinase (0.01-0.5 microM) and both are antagonized by high concentrations of Ca2+ and CaM. The Ca2+-requirement for obtaining half maximal concentration is shifted from 1.1 microM to 6.3 microM Ca2+ in the presence of 0.5 microM cAMP-kinase. These data indicate that the response of the contractile apparatus to a change in the free [Ca2+] can be modulated by cAMP-kinase at the level of the contractile proteins. It is further suggested that the tone of coronary smooth muscle is determined by the relative and not by the absolute concentrations of Ca2+, CaM and cAMP-kinase.