Protein kinase C (PKC) and the
ATP-dependent K+
channel (KATP channel) have been implicated in the mechanism of ischemic preconditioning in animal models. This study investigated the role of
KATP channels and PKC in preconditioning in human myocardium and whether
KATP channels are activated via a PKC-dependent pathway. Right atrial trabeculae were superfused with
Tyrode's solution and paced at 1 Hz. After stabilization, muscles underwent one of nine different protocols, followed by simulated
ischemia (SI) consisting of 90 minutes of hypoxic substrate-free superfusion paced at 3 Hz and then by 120 minutes of reperfusion. Preconditioning consisted of 3 minutes of SI and 7 minutes of reperfusion. The experimental end point was recovery of contractile function after SI, presented here as percentage recovery (%Rec) of baseline function. %Rec was significantly improved by preconditioning by the
KATP channel opener
cromakalim (CK), and by the PKC activator
1,2-dioctanoyl-sn-glycerol (DOG) compared with nonpreconditioned controls when these treatments were given before the SI insult (control group, 29.5 +/- 3.6%; preconditioned group, 63.5 +/- 5.4%, CK-treated group, 52.9 +/- 3.1%; and DOG-treated group, 48.0 +/- 3.5%; P < .01). The effects of CK could be blocked by the
KATP channel blocker
glibenclamide (%Rec, 17.8 +/- 3.5%). Preconditioning could be blocked by the PKC antagonist
chelerythrine (%Rec, 24.1 +/- 5.0%) and the KATP blocker
glibenclamide (%Rec, 24.8 +/- 3.1%). The effects of DOG could also be blocked by
glibenclamide (%Rec, 23.1 +/- 2.3%).(ABSTRACT TRUNCATED AT 250 WORDS)