Regulation of smooth muscle actin-myosin interaction and force by calponin

Smooth muscle contraction is regulated primarily by the reversible phosphor ylation of myosin triggered by an increase in sarcoplasmic tree Ca2+ concen tration ([Ca2+](i)). Contraction can, however, be modulated by other signal transduction pathways, one of which involves the thin filament-associated protein calponin. The hi (basic) isoform of calponin binds to actin with hi gh affinity and is expressed specifically in smooth muscle at a molar ratio to actin of 1 : 7. Calponin inhibits (i) the actin-activated MgATPase acti vity of smooth muscle myosin (the cross-bridge cycling rate) via its intera ction with actin, (ii) the movement of actin filaments over immobilized myo sin in the in vitro motility assay, and (iii) force development or shorteni ng velocity in permeabilized smooth muscle strips and single cells. These i nhibitory effects of calponin can be alleviated by protein kinase C (PKC)ca talysed phosphorylation and restored following dephosphorylation by a type 2A phosphatase. Three physiological roles of calponin can be considered bas ed on its in vitro functional properties: (i) maintenance of relaxation at resting [Ca2+]i, (ii) energy conservation during prolonged contractions, an d (iii) Ca2+-independent contraction mediated by phosphorylation of calponi n by PKC epsilon, a Ca2+-independent isoenzyme of PKC.