Connexin 43 in ischemic pre- and postconditioning.
Connexin 43 (Cx43) is the predominant protein forming gap junctions and non-junctional hemichannels in ventricular myocardium, but Cx43 is also localized at the inner membrane of cardiomyocyte mitochondria. In cardiomyocytes, Cx43 is involved in the formation of reactive oxygen species, which are central to the signal transduction cascade of ischemic preconditioning's protection. Accordingly, genetically-induced or age-related loss of Cx43 abolishes infarct size reduction by ischemic preconditioning. Similarly, mitochondrial import inhibition of Cx43 completely blocks infarct size reduction by pharmacological preconditioning with diazoxide. In contrast to its importance for preconditioning-induced cardioprotection, Cx43 is not important for infarct size reduction by ischemic postconditioning. In summary, Cx43--especially Cx43 localized in mitochondria--appears to be one key element of the signal transduction cascade of the protection by preconditioning.
Schulz
Rainer
R
Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Boengler
Kerstin
K
Totzeck
Andreas
A
Luo
Yukun
Y
Garcia-Dorado
David
D
Heusch
Gerd
G
D018031:Connexin 43 / Q000502:physiology*; D003981:Diazoxide; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008928:Mitochondria; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000517:prevention & control*; D009206:Myocardium; D032383:Myocytes, Cardiac; D015398:Signal Transduction; D013997:Time Factors
D018031:Connexin 43; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D003981:Diazoxide