Isosteviol Sensitizes sarcK(ATP) Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes

K(ATP) channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of K(ATP) channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarcK(ATP) channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarcK(ATP) channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria.