New, emerging roles for cardiac connexins. Mitochondrial Cx43 raises new questions.

Connexins are protein subunits that constitute the gap junction channel, a dodecameric channel connecting two neighbouring cells formed by two hexameric hemichannels provided by either cell. The gap junction channel permits intercellular communication by allowing the propagation of the action potential and the transfer of small molecules such as cAMP. Six different gap junctional proteins (connexins; Cx) have been identified in the cardiovascular system: Cx31.9, Cx37, Cx40, Cx43, Cx45, Cx46, Cx50, and Cx57 (the molecular mass in kDa is given by the number) [1,2]. In the heart, there are mainly three isoforms that differ in their molecular weight: connexin 43 (a 43-kDa connexin; Cx43), which is found in most parts of the heart; connexin 40 (Cx40), which is mainly expressed in atria and in the conduction system; and connexin 45 (Cx45), which is expressed predominantly in embryonic stages and has been identified in parts of the ventricular conduction system of mice and rats [3]. Moreover, Cx45 was shown to be expressed in co-cultures of neonatal rat cardiomyocytes with fibroblasts [4] and is involved in myocyte/fibroblast coupling in the sinoatrial node [5]. Cx50 has been found in valvular tissue of the rat heart [6]. Connexins have four transmembrane regions, one intracellular and two extracellular loops, and intracellular Nand C-terminal tails. The length of the C-terminus differs among the various isoforms and is subject to phosphorylation by a number of kinases (for review, see Ref. [2]). Connexins are synthesized in the rough endoplasmic reticulum, folded, and transported to the Golgi apparatus within vesicles. In the