Stimulation of cardiac beta-adrenoceptors targets connexin 43.

Connexin 43 (Cx43) is the major protein of cardiac ventricular gap junctions and is crucial to cell-cell communication and cardiac function. The protein level of Cx43 is reduced in patients with heart failure or dilated cardiomyopathy (DCM), pathophysiological conditions often associated with arrhythmias. As catecholamines are often increased in cardiac diseases, Salameh et al., in this issue of the BJP, investigated the effect of beta-adrenoceptor stimulation of neonatal cardiomyocytes on Cx43 expression and found increased Cx43 mRNA and protein levels following 24 h stimulation. Up-regulation of Cx43 was associated with phosphorylation of mitogen-activated protein kinases and translocation of transcription factors into the nucleus. In patients with DCM, a situation often associated with desensitization of the beta-adrenoceptor system, Cx43 expression was reduced. The characterization of the signal transduction pathways involved in Cx43 expression and intracellular localization in human myocardium in vivo is a promising target for the development of new anti-arrhythmic strategies.