抄録
It has been known that intracellular acidification leads to gap junction channel closure. This phenomenon is called "chemical gating", which may be one of the causes of lethal arrhythmia during cardiac ischemia. Chemical regulation of Cx43 follows a ball-and-chain model, in which the carboxyl terminal (CT) domain acts as a gating particle that binds to a receptor affiliated with the pore. However, the location of the "receptor" for the CT has been unknown.Electrophysiological analysis shows that Cx43 channels reside in three states; closed (C), open (O) or residual (R). Since the R state is eliminated by truncation of the CT, it is hypothesized that the R state results from the interaction of the CT with the receptor. Recently, we showed in vitro that there is an intramolecular interaction of the CT with a region in the cytoplasmic loop of Cx43 (amino acids 119-144; dubbed "L2"). To determine the function of the L2, Cx43 channels were recorded in the presence of a peptide corresponding to the L2 region, delivered via the patch pipette. This manipulation eliminated the R state in a manner similar to that observed after truncation of the CT, indicating that L2 peptide competitively inhibits the interaction between the CT and the native L2 region. Thus, we propose that the L2 acts as a "receptor" that interacts with the CT during channel gating. [J Physiol Sci. 2006;56 Suppl:S29]
