title: Ca2+ clearance and contractility in vascular smooth muscle: evidence from gene-altered murine models.
abstract: The central importance of calcium clearance proteins, and their regulators, in the modulation of myocardial contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) has long been established. Key players identified include the Na(+)-Ca(2+) exchanger, the Na(+)-K(+) ATPase, the sarco(endo)plasmic reticulum Ca(2+)-ATPase and associated phospholamban. Gene-targeted and transgenic murine models have been critical in the elucidation of their function. The study of these proteins in the regulation of contractile parameters in vascular smooth muscle, on the other hand, is less well studied. More recently, gene-targeted and transgenic models have expanded our knowledge of Ca(2+) clearance proteins and their role in both tonic and phasic smooth muscle contractility. In this review, we will briefly treat the mechanisms which underlie Ca(2+) clearance in smooth muscle. These will be addressed in light of studies using gene-modified mouse models, the results of which will be compared and contrasted with those in the cardiomyocyte. The recently identified human mutations in phospholamban, which lead to dilated cardiomyopathy, are also present in vascular and other smooth muscle. Given the importance of these Ca(2+) clearance systems to modulation of smooth muscle, it is likely that mutations will also lead to smooth muscle pathology.
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0576, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Oloizia
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Paul
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008955:Models, Cardiovascular; D008957:Models, Genetic; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*
chemical_list: D002118:Calcium