Persistence of gap junction communication during myocardial ischemia.
During myocardial ischemia, severe ATP depletion induces rigor contracture followed by intracellular Ca2+ concentration ([Ca2+]i) rise and progressive impairment of gap junction (GJ)-mediated electrical coupling. Our objective was to investigate whether chemical coupling through GJ allows propagation of rigor in cardiomyocytes and whether it persists after rigor development. In end-to-end connected adult rat cardiomyocytes submitted to simulated ischemia the interval between rigor onset was 3.7 +/- 0.7 s, and subsequent [Ca2+]i rise was virtually identical in both cells, whereas in nonconnected cell pairs the interval was 71 +/- 12 s and the rate of [Ca2+]i rise was highly variable. The GJ blocker 18alpha-glycyrrhetinic acid increased the interval between rigor onset and the differences in [Ca(2+)]i between connected cells. Transfer of Lucifer yellow demonstrated GJ permeability 10 min after rigor onset in connected cell pairs, and 30 min after rigor onset in isolated rat hearts submitted to nonflow ischemia but was abolished after 2 h of ischemia. GJ-mediated communication allows propagation of rigor in ischemic myocytes and persists after rigor development despite acidosis and increased [Ca2+]i.
Ruiz-Meana
M
M
Department of Cardiology, Hospital General Vall d'Hebron, Barcelona 08035, Spain.
Garcia-Dorado
D
D
Lane
S
S
Pina
P
P
Inserte
J
J
Mirabet
M
M
Soler-Soler
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005456:Fluorescent Dyes; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid; D002118:Calcium