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

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Abstract

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, K d (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 K i, the ATP concentration causing half-maximal inhibition, from 70 μM in control (n=7) to 232 μM (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 K I in excised membrane patches and high levels of intracellular ATP concentration during myocardial ischemia or hypoxia.

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Correspondence to Yung E. Earm.

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Ban, J., So, I., Kim, E.-. et al. ATP-sensitive potassium channels are modulated by intracellular lactate in rabbit ventricular myocytes. Pflugers Arch. 425, 546–548 (1993). https://doi.org/10.1007/BF00374883

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Key words

  • lactate
  • ATP-sensitive potassium channel
  • rabbit ventricular myocytes
  • inside-out patch-clamp technique
  • myocardial ischemia