SM22 alpha is required for agonist-induced regulation of contractility: Evidence from SM22 alpha knockout mice

Abstract

The present study was undertaken to determine whether SM22 alpha participates in the regulation of vascular smooth muscle contractility using SM22 alpha knockout mice and, if so, to investigate the mechanisms involved. Aortic ring preparations were mounted and equilibrated in organ baths for 60 min before observing contractile responses to 50 mM KCI, and then exposed to contractile agents such as phenylephrine and phorbol ester. Measurement of isometric contractions using a computerized data acquisition system was combined with molecular or cellular experiments. Interestingly, the aortas from SM22 alpha-deficient mice (SM22(-1-Lacz)) displayed an almost three-fold increase in the level of SM22 beta protein compared to wild-type mice, but no change in the levels of caldesmon, actin, desmin or calponin. Ca2+-independent contraction in response to phenylephrine or phorbol ester was significantly decreased in the SM22 alpha-deficient mice, whereas in the presence of Ca2+ neither contraction nor subcellular translocation of myosin light chain kinase (MLCK) in response to phenylephrine or 50 mM KCI was significantly affected. A decrease in phosphorylation of extracellular signal regulated kinase (ERK) 1/2 was observed in the SM22 alpha -deficient mice and this may be related to the decreased vascular contractility. Taken together, this study provides evidence for a pivotal role of SM22 alpha in the regulation of Ca2+ -independent vascular contractility.