The tail of Cx43: its crucial protective role in acute myocardial infarction

In the heart, synchronized contractile activity is facilitated by gap junctions, intercellular channels that underlie electrical and molecular communications between cardiac myocytes. In the ventricles of the mammalian heart, gap junctions are predominately constructed of connexin43 (Cx43) subunits. In heterozygous Cx43 knockout (Cx43/KO) mice, expression of Cx43 is roughly halved and electrical conduction in the ventricles is impaired.1 Cx43/KO mice have increased susceptibility to arrhythmias after acute myocardial infarction (MI).2Although low-resistance communication is typically desirable, a reduction of intercellular conduction during ischaemia–reperfusion episodes can be beneficial by limiting the spread of toxic metabolites that promote tissue damage.3 Decoupling the gap junctions during acute ischaemia has been shown to reduce infarct size,4 and Cx43/KO mice are reported to have smaller infarcts than their wild-type counterparts.5 Conduction via gap junctions can be post-transcriptionally regulated by the phosphorylation of various amino acids6 and by pH,7 both of which are dependent on the carboxyl terminal (CT) domain of Cx43.Maass et al. demonstrate that loss of the CT domain of Cx43 results in gap junctions that are no longer chemically regulated during ischaemia–reperfusion episodes. They show that this leads to an increased infarct size and an increased susceptibility to arrhythmias.8 To do this, they used a … *Corresponding author. Tel: +1 216 445 7823; fax: +1 216 445 4166, E-mail address : chengy{at}ccf.org