ATP-sensitive potassium channels are modulated by intracellular lactate in rabbit ventricular myocytes

During myocardial ischemia, increased anaerobic glycolysis results in the accumulation of large amount of intracellular lactate. Effects of lactate on the ATP-sensitive potassium (KATP) channels were examined in rabbit ventricular myocytes, using the inside-out patch-clamp technique. Millimolar concentrations of lactate, applied to the cytosolic side of the patch membrane, induced openings of the KATP channel. This effect was inhibited by 0.1 mM glybenclamide. Lactate-induced openings of the channel were increased in a dose-dependent fashion. In dose-response relation for lactate, Kd (the lactate concentration producing half-maximal activation) and n (Hill coefficient) were 20 mM and 1.3, respectively (n = 5). Activation of KATP channels by lactate occurred even in the presence of 2 mM ATP. Lactate also caused a significant increase in Ki, the ATP concentration causing half-maximal inhibition, from 70 microM in control (n = 7) to 232 microM (n = 5). From the above results it could be concluded that intracellular lactate modulate KATP channels directly and such modulation may resolve the discrepancy between the low Ki in excised membrane patches and high levels of intracellular ATP concentration during myocardial ischemia or hypoxia.