Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders

Regulation of cell-to-cell communication in the heart by the gap junction protein Connexin43 (Cx43) involves modulation of Cx43 phosphorylation state by protein kinases, and dephosphorylation by protein phosphatases. Dephosphorylation of Cx43 has been associated with impaired intercellular coupling and enhanced arrhythmogenesis in various pathologic states. While there has been extensive study of the protein kinases acting on Cx43, there has been limited studies of the protein phosphatases that may underlie Cx43 dephosphorylation. The focus of this review is to introduce serine-threonine protein phosphatase regulation of Cx43 phosphorylation state and cell-to-cell communication, and its impact on arrhythmogenesis in the setting of chronic heart failure and myocardial ischemia, as well as on atrial fibrillation. We also discuss the therapeutic potential of modulating protein phosphatases to treat arrhythmias in these clinical settings.