Pathological remodeling of cardiac gap junction connexin 43—With special reference to arrhythmogenesis

• Published in: Pathophysiology (Amsterdam) 2010-04, Vol.17 (2), p.73-81
• Main Author: Imanaga, Issei
• Format: Article
• Language: English
• Subjects: Arrhythmogenesis; Cardiac gap junction; Remodeling of Cx43
• ISSN: 0928-4680; 1873-149X
• DOI: 10.1016/j.pathophys.2009.03.013

A dysfunction of the cardiac gap junction, which contributes to electrical cell-to-cell coupling is one of essential factors known to generate arrhythmias. The function of the gap junction depends on the regulation of connexin which composes the gap junction channel. A dysfunction of the gap junction is possibly caused by the down-regulation of connexin. In this review, the relationship between pathological remodeling of connexin 43 (Cx43) and susceptibility of the heart to the ventricular fibrillation, which is a lethal ventricular tachyarrhythmia, is addressed. A suppression of the PKA-mediated phosphorylation or an augmentation of the PKC-mediated phosphorylation of Cx43 induces the downward remodeling of Cx43. Factors regarding downward remodeling of Cx43, such as hypoxia (including intracellular Ca overload and intracellular acidosis), angiotensin II or an activation of PKCɛ make the heart more susceptible to the ventricular fibrillation, while factors regarding upward remodeling of Cx43, such as cyclic AMP or an activation of PKA, lower susceptibility. As a result, from a clinical point of view, angiotensin II antagonists (synthesis inhibitors or receptor blockades), PKC inhibitors or PKA activators are thus considered to provide a therapeutic approach for the treatment of the initiation or advancement of the ventricular fibrillation.