Glycolytic pathway intermediates activate cardiac ryanodine receptors

Abstract

During myocardial ischaemia and reperfusion, enhancement of glycolytic activity occurs and this may lead to fluctuating levels of glycolytic intermediates. We demonstrate that sugar phosphate intermediates of glycolysis, particularly fructose-1,6-diphosphate (FDP; 100 microM-10 mM), can activate sheep cardiac ryanodine receptor (RyR) channels incorporated into bilayers (open probability (Po) increases up to approximately 0.6) and stimulate [3H]ryanodine binding (> 200%) to isolated cardiac sarcoplasmic reticulum (SR) membrane vesicles. The relative effectiveness of the sugar phosphates in stimulating [3H]ryanodine binding and increasing the Po of the channels was FDP > glucose-1-phosphate (G-1-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.