The Cytosolic Calcium-Force Relation of Vascular Smooth Muscle during the Contraction and the Relaxation

Abstract

The contraction of vascular smooth muscle is regulated mainly by changes in the cytosolic calcium concentration ([Ca²⁺]i), and thus development of force has been regarded as a good indicator of an increase in [Ca²⁺]i [1]. The contraction is initiated by an increase in [Ca²+]i and the subsequent phosphorylation of the myosin light chain by the complex of Ca²⁺-calmodulin and myosin light chain kinase [2]. It has been demonstrated that, for a given elevation of [Ca²⁺]i, the receptor-mediated stimulation by various agonists caused a proportionally greater force development than did the depolarization with high K⁺ solutions [3–8]. While it is generally accepted that the force development mainly depends on Ca²⁺-mediated myosin light chain phosphorylation, it has been demonstrated that force development could be maintained under lower levels of [Ca²⁺]i and myosin light chain phosphorylation through other Ca²⁺-insensitive mechanisms such as latch bridges [9] or cooperating cycling of cross-bridges [10]. Using receptor-coupled per-meabilized vascular smooth muscle with staphylococcal α-toxin [11] and β-escin [12], it was demonstrated that the Ca²⁺ sensitivity of the contractile apparatus is modulated by the receptor-G-protein-coupled mechanism. A protein kinase C-mediated mechanism was proposed to explain the agonist-modulated Ca²⁺ sensitivity of vascular smooth muscle contractility [6–8].