The FASEB Journal • Research Communication Mechanisms of cardiac protection from ischemia/reperfusion injury: a role for caveolae and caveolin-1

ABSTRACT Caveolae, small invaginations in the plasma membrane, contain caveolins (Cav) that scaf-fold signaling molecules including the tyrosine kinase Src. We tested the hypothesis that cardiac protection involves a caveolin-dependent mechanism. We used in vitro and in vivo models of ischemia-reperfusion injury, electron microscopy (EM), transgenic mice, and bio-chemical assays to address this hypothesis. We found that Cav-1 mRNA and protein were expressed in mouse adult cardiac myocytes (ACM). The volatile anesthetic, isoflurane, protected ACM from hypoxia-induced cell death and increased sarcolemmal caveolae. Hearts of wild-type (WT) mice showed rapid phosphorylation of Src and Cav-1 after isoflurane and ischemic precondi-tioning. The Src inhibitor PP2 reduced phosphoryla