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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Coetzee WA (1992) Regulation of ATP sensitive potassium channel of isolated guinea pig ventricular myocytes by sarcolemmal monocarboxylate transport. Cardiovasc Res 26: 1077–1086
Earm YE, Ho WK, So IS (1990) Inward current generated by Na-Ca exchange during the action potential in single atrial cells of the rabbit. Proc R Soc Lond B 240: 61–81
Elliott AC, Smith CGL, Allen DG (1989) Simultaneous measurements of action potential duration and intracellular ATP in isolated ferret hearts exposed to cyanide. Circ Res 64: 583–591
Findlay I (1988) Effects of ADP upon the ATP-sensitive K+ channel in rat ventricular myocytes. J Memb Biol 101: 83–92
Findlay I, Faivre JF (1991) ATP-sensitive K+ channel in heart muscle. FEBS Lett 279: 95–97
Janse MJ, Wit AL (1989) Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 69: 1049–1169
Keung EC, Li Q (1991) Lactate activate ATP-sensitive potassium channels in guinea pig ventricular myocytes. J Clin Invest 85: 950–954
Lederer WJ, Nichols CG (1989) Nucleotide modulation of the activity of rat heart ATP-sensitive K+ channels in isolated membrane patches. J Physiol(Lond) 419: 193–211
Neely JR, Grotyohann LW (1984) Role of glycolytic products in damage to ischemic myocardium. Circ Res 55: 816–824
Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature(Lond) 305: 147–148
Rovetto MJ, Whitmer JT, Neely JR (1973) Comparison of the effects of anoxia and whole heart ischemia on carbohydrate utilization in isolated working hearts. Circ Res 32: 699–711
Tung RT, Kurachi Y (1991) On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig. J Physiol(Lond) 437: 239–256
Weiss JN, Lamp ST (1989) Cardiac ATP-sensitive K+ channels: evidence for preferential regulation by glycolysis. J Gen Physiol 94: 911–935
About this article
Cite this article
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
- ATP-sensitive potassium channel
- rabbit ventricular myocytes
- inside-out patch-clamp technique
- myocardial ischemia