SM22α Is Required for Agonist-induced Regulation of Contractility: Evidence from SM22α Knockout Mice

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 KCl, 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 ($SM22^{-/-LacZ}$) 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. $Ca^{2+}$-independent contraction in response to phenylephrine or phorbol ester was significantly decreased in the $SM22{\alpha}$-deficient mice, whereas in the presence of $Ca^{2+}$ neither contraction nor subcellular translocation of myosin light chain kinase (MLCK) in response to phenylephrine or 50 mM KCl 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 $Ca^{2+}$-independent vascular contractility.