The L-Type Ca+ and KATP channels may contribute to pacing-induced protection against anoxia-reoxygenation in the embryonic heart model.
L-Type Ca(2+) and K(ATP) Channels in Pacing-Induced Cardioprotection.


OBJECTIVE
The L-type Ca(2+) channel, the sarcolemmal (sarcK(ATP)), and mitochondrial K(ATP) (mitoK(ATP)) channels are involved in myocardial preconditioning. We aimed at determining to what extent these channels can also participate in pacing-induced cardioprotection.


METHODS
Hearts of 4-day-old chick embryos were paced in ovo during 12 hour using asynchronous intermittent ventricular stimulation at 110% of the intrinsic rate. Sham operated and paced hearts were then submitted in vitro to anoxia (30 minutes) and reoxygenation (60 minutes). These hearts were exposed to L-type Ca(2+) channel agonist Bay-K-8644 (BAY-K) or blocker verapamil, nonselective K(ATP) channel antagonist glibenclamide (GLIB), mitoK(ATP) channel agonist diazoxide (DIAZO), or antagonist 5-hydroxydecanoate. Electrocardiogram, electromechanical delay (EMD) reflecting excitation-contraction (E-C) coupling, and contractility were determined.


RESULTS
Under normoxia, heart rate, QT duration, conduction, EMD, and ventricular shortening were similar in sham and paced hearts. During reoxygenation, arrhythmias ceased earlier and ventricular EMD recovered faster in paced hearts than in sham hearts. In sham hearts, BAY-K (but not verapamil), DIAZO (but not 5-hydroxydecanoate) or GLIB accelerated recovery of ventricular EMD, reproducing the pacing-induced protection. By contrast, none of these agents further ameliorated recovery of the paced hearts.


CONCLUSIONS
The protective effect of chronic asynchronous pacing at near physiological rate on ventricular E-C coupling appears to be associated with subtle activation of L-type Ca(2+) channel, inhibition of sarcK(ATP) channel, and/or opening of mitoK(ATP) channel.
Department of Physiology, Faculty of Biology and Medicine, University Hospital, Lausanne, Switzerland.
Philippe
P
Bruchez
Alexandre
A
Sarre
Lukas
L
Kappenberger
Eric
E
Raddatz
D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D002642:Chick Embryo; D004195:Disease Models, Animal; D005311:Fetal Hypoxia / Q000378:metabolism* / Q000517:prevention & control*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000196:embryology / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D016896:Treatment Outcome
D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel