Abstract
In cardiac muscle, the gap junction greatly contributes to intercellular impulse propagation. The remodeling of the gap junction is induced in pathological myocardium and influences the cardiac function. We investigated remodeling of connexin 43 (Cx43) which is dominant in the ventricular muscle cells, in reference to phosphorylation and dephosphorylation of the protein, using methods of electrophysiology, immuno blot and immunohistochemistry in adult guinea-pig and rat hearts.An activation of PKA promoted the PKA-mediated phosphorylation of Cx43 in association with an increase in the electrical intercelluar coupling and in expression of Cx43. In hypoxia, intracellular Ca-overload or acidosis, the PKA-mediated phosphorylation of Cx43 was inhibited in association with a suppression of the intercellular coupling and of expression of Cx43. These deteriorated changes of Cx43 were alleviated by PKA-activators. In the diabetic or PMA-treated heart, the PKC-mediated phosphorylation of Cx43 was augmented in association with an inhibition of the intercellular coupling and of expression of Cx43. These effects of an activation of PKC were ameliorated by a treatment of PKC-inhibitors, proteasome inhibitors or lysosome inhibitors. These results indicate that Cx43 hyperphosphorylated by PKC is highly susceptible to proteolytic degradation. It is concluded that Cx43 is up-regulated by PKA and down-regulated by PKC, and the remodeling of Cx43 is essentially induced by an excess activation of PKC. [J Physiol Sci. 2006;56 Suppl:S29]
