Glycolytic pathway intermediates activate cardiac ryanodine receptors

During myocardial ischaemia and reperfusion, enhancement of glycolytic activity occurs and this may lead to fluctuating levels of glycolytic intermediates [1-3]. We demonstrate that sugar phosphate intermediates of glycolysis, particularly fructose-1,6-diphosphate (FDP; 100 mu M-10 mM), can activate sheep cardiac ryanodine receptor (RBR) channels incorporated into bilayers (open probability (Po) increases up to approximately 0.6) and stimulate [H-3]ryanodine binding (>200%) to isolated cardiac sarcoplasmic reticulum (SR) membrane vesicles. The relative effectiveness of the sugar phosphates in stimulating [H-3]ryanodine binding and increasing the Po of the channels mas FDP > glucose-1-phosphate (G-6-P) > fructose-6-phosphate (F-6-P) > glucose-6-phosphate (G-6-P). These novel properties of the sugar phosphate compounds indicate that changes in glycolytic flux may influence the release of SR Ca2+ by modulating RyR channel gating. (C) 1998 Federation of European Biochemical Societies.