High glucose protects single beating adult cardiomyocytes against hypoxia.
In the heart, the opening of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels seems to be crucial for the cardiac protection against hypoxia/ischaemia. In the present study, we have exposed cardiomyocytes under hypoxia to high extracellular glucose (30 mM). Under these conditions, intracellular concentration of 1,3-bisphosphoglycerate has increased confirming stimulation of glycolysis. Perforated patch-clamp electrophysiology revealed that hypoxia induces whole-cell K(+) current in cardiomyocytes more efficiently in the presence than in the absence of high glucose. Glucose significantly promoted survival of cardiomyocytes exposed to hypoxia. HMR 1098, an antagonist of sarcolemmal K(ATP) channels, inhibited glucose-induced activation of whole-cell K(+) current during hypoxia as well as glucose-mediated cytoprotection. An inhibitor of glyceraldehyde 3-phosphate dehydrogenase, iodoacetate, inhibited glycolysis in hypoxia and blocked the activation of sarcolemmal K(ATP) channels. Based on the obtained results, we conclude that the activation of sarcolemmal K(ATP) channels is involved in glucose-mediated cardioprotection.
Jovanović
Sofija
S
Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
Jovanović
Nenad
N
Jovanović
Aleksandar
A
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005947:Glucose / Q000008:administration & dosage*; D006019:Glycolysis / Q000187:drug effects; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*
D002316:Cardiotonic Agents; D015221:Potassium Channels; D005947:Glucose; D011188:Potassium