Role of the gap junction in ischemic preconditioning in the heart.
The gap junction plays roles not only in electrical coupling of cardiomyocytes but also in intercellular transport of biologically active substances. Furthermore, the gap junction participates in decision making on cell survival versus cell death in various types of cells, and a part of reperfusion injury in the heart has been indicated to be gap junction mediated. The contribution of gap junction communication (GJC) and/or mitochondrial "hemichannels" to protective signaling during the trigger phase of ischemic preconditioning (IPC) is suggested by observations that IPC failed to protect the heart when GJC was blocked during IPC. Although ischemia suppresses both electrical and chemical GJC, chemical GJC persists for a considerable time after electrical GJC is lost. IPC facilitates the ischemia-induced suppression of chemical GJC, whereas IPC delays the reduction of electrical GJC after ischemia. The inhibition of GJC during sustained ischemia and reperfusion by GJC blockers mimics the effect of IPC on myocardial necrosis. IPC induces distinct effects on the interaction of connexin-43 with protein kinases, and the phosphorylation of connexin-43 at Ser368 by PKCepsilon is a primary mechanism of inhibition of chemical GJC by IPC. Several lines of evidence support the notion that the modulation of GJC is a part of the mechanism of IPC-induced protection against myocardial necrosis and arrhythmias, though what percentage of IPC protection is attributable to the inhibition of GJC during ischemia-reperfusion still remains unclear.
Miura
Tetsuji
T
Second Dept. of Internal Medicine, Sapporo Medical Univ., Japan. miura@sapmed.ac.jp
Miki
Takayuki
T
Yano
Toshiyuki
T
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000502:physiology*