Pharmacological studies of K+ loss from ischaemic myocardium in vitro: roles of ATP-dependent K+ channels and lactate-coupled efflux.
Perfused guinea-pig hearts were rendered ischaemic by 95% reductions in coronary flow. K+ and lactate release over the first 6 min of ischaemia were reduced by glibenclamide (described as a K+ATP channel blocker), 2-deoxyglucose (inhibitor of lactate synthesis) and alpha-cyano-4-hydroxycinnamic acid (inhibitor of lactate transport). Glibenclamide did not selectively reduce K+ loss without affecting lactate release, as would be expected for a selective K+ATP channel blocker. During a single 30 min period of ischaemia, a secondary release of K+ was observed corresponding to the onset of ventricular fibrillation, with no associated increase in lactate efflux, which appeared sensitive to glibenclamide. In conclusion, glibenclamide failed to reduce K+ loss in early ischaemia without reducing lactate release as would be expected for a selective K+ATP channel blocker. Caution should be exercised when using glibenclamide as a specific blocker of K+ATP channels in the absence of measurements of metabolic parameters.
Gwilt
M
M
ZENECA Pharmaceuticals, Macclesfield, Cheshire, UK.
Norton
B
B
Henderson
C G
CG
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003373:Coumaric Acids / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000378:metabolism
D003373:Coumaric Acids; D007773:Lactates; D015221:Potassium Channels; C007175:alpha-cyano-4-hydroxycinnamate; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D011188:Potassium; D005905:Glyburide