Cx43 phosphorylation and cardioprotection

Connexin-43 (Cx43), a transmembrane protein able to oligomerize into hexamers around a central pore, is the main protein-forming gap junctional channels in ventricular cardiomyocytes. Altered Cx43 expression or distribution has been shown to impair propagation of electrical impulses and promote arrhythmias during ischaemia and reperfusion.1 However, in the past few years, it has become evident that the role of Cx43 in myocardial ischaemia pathophysiology goes beyond its role in arrhythmogenesis. Gap junction uncouplers have been shown to limit infarct size after ischaemia in different tissues, including heart2 and brain,3 thus supporting a role for gap junctions in intercellular spreading of injury during ischaemia–reperfusion. These findings were further strengthened by studies in heterozygous Cx43-deficient mice (Cx43+/−) submitted to chronic ischaemia without reperfusion,4 which showed reduced infarctions in mutant animals. However, the involvement of Cx43 in the pathophysiology of ischaemia–reperfusion injury is not restricted to the spreading of injury, and several studies suggest an important role in cardioprotection.5,6In this context, the study by Srisakuldee et al. 7 adds important information on the cardioprotective role of Cx43. The authors demonstrate that both ischaemic preconditioning and pretreatment with diazoxide are able to induce, in isolated rat hearts, specific phosphorylation of … *Corresponding author. Tel: +34 93 489 4134; fax: +34 934894032. E-mail address : arodriguez{at}ir.vhebron.net