Preconditioning in the absence or presence of sustained ischemia modulates myocardial Cx43 protein levels and gap junction distribution.
In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts. We also compared the effect of sustained ischemia with or without PC on Cx43 spatial distribution. In experiments with PC only, there was an initial decrease in Cx43 levels within the ischemic zone followed by a progressive increase after 48 h reperfusion. End-to-end immunolabeling of Cx43 was augmented in the ischemic region between 24 and 48 h reperfusion; labeling was not uniquely confined to myocyte abutments, but was also dispersed along the sarcolemma. Cx43 immunolabelling was more intense and diffuse in hearts subjected to PC before sustained coronary occlusion (compared to non-PC). These data indicate that gap junctions are significantly altered during brief episodes of ischemia. Reorganization of the gap junction complex could contribute to PC-mediated reductions in cardiac arrhythmias.
Daleau
P
P
Quebec Heart Institute, Laval Hospital, Ste-Foy, Canada.
Boudriau
S
S
Michaud
M
M
Jolicoeur
C
C
Kingma
J G
JG
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D015151:Immunoblotting; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008856:Microscopy, Fluorescence; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits
D018031:Connexin 43