Calponin decreases the rate of cross-bridge cycling and increases maximum force production by smooth muscle myosin in an in vitro motility assay.

Abstract

Mammalian smooth muscles, like invertebrate "catch" muscles, dynamically regulate the rate of cross-bridge cycling. During sustained contractions, cross-bridge cycling rates may decrease severalfold, whereas tension remains elevated ("latch-state"). Physiologic studies have shown that decreased cycling rate is frequently, but not always, associated with dephosphorylation of the 20,000-dalton light chain of myosin. Tropomyosin, caldesmon, and calponin are actin-binding proteins found in mammalian smooth muscles that modulate actin-activated myosin ATPase activity in vitro and may modulate cross-bridge cycling in situ. Using an in vitro motility assay in combination with a new method for estimating relative changes in the force exerted on actin filaments, the present study demonstrates that the effects of calponin on actin filament motility are: increased actin filament binding to thiophosphorylated smooth muscle myosin, decreased filament velocity from 2.0 to 0.74 microns/s, and a 3-4-fold increase in the force exerted on stationary actin filaments. Taken together, these observations suggest that calponin inhibits the rate of dissociation of the high-affinity actomyosin complex and, consequently, that it may be an integral component of the latch-state in mammalian smooth muscles.