Glycolytic pathway intermediates activate cardiac ryanodine receptors

FEBS Letters

Sitsapesan, Rebecca¹  Williams, Alan J.¹  Chan, Wei Mun¹  Kermode, Helen¹ 

[1] Cardiac Medicine, NHLI, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK

关键词: Ryanodine receptor;    Ca2+-release channel;    Sarcoplasmic reticulum;    Glycolysis;    Ischemia;    Fructose-1;    6-diphosphate;   

DOI  :  10.1016/S0014-5793(98)00725-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM–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.

【 授权许可】

Unknown