STRUCTURE OF CONNEXIN43 AND ITS REGULATION BY PH(I)

pH(i) Regulation of Connexin43. Electrical coupling in the heart provi des an effective mechanism for propagating the cardiac action potentia l efficiently throughout the entire heart, Cells within the heart are electrically coupled through specialized membrane channels called gap junctions, Studies have shown that gap junctions are dynamic, carefull y regulated channels that are important for normal cardiogenesis. We h ave recently been interested in the molecular mechanisms by which intr acellular acidification leads to gap junction channel closure, Previou s results in this lab have shown that truncation of the carboxyl termi nal (CT) of connexin43 (Cx43) does not interfere with functional chann el expression, Further, the pH-dependent closure of Cx43 channels is s ignificantly impaired by removal of this region of the protein, Other studies have shown that the CT is capable of interacting with its rece ptor even when not covalently attached to the channel protein, From th ese data we have proposed a particle-receptor model to explain the pH- dependent closure of Cx43 gap junction channels, Detailed analysis of the CT has revealed interesting new information regarding its possible structure, Here we review the most recent studies that have contribut ed to our understanding of the molecular mechanisms of regulation of t he cardiac gap protein Cx43.