The L-Type Ca2+ and KATP Channels May Contribute to Pacing-Induced Protection Against Anoxia-Reoxygenation in the Embryonic Heart Model

L-Type Ca2+ and K-ATP Channels in Pacing-Induced Cardioprotection. Aims: The L-type Ca2+ 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 Ca2+ 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. Conclusion: 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 Ca2+ channel, inhibition of sarcK(ATP) channel, and/or opening of mitoK(ATP) channel. (J Cardiovasc Electrophysiol, Vol. 19, pp. 1196-1202, November 2008).