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ATP is normally available in cells at millimolar concentrations and is "buffered" by intracellular pools of other high-energy phosphates, such as creatine phosphate. Thus intracellular ATP ( ATPi) may seem an unlikely candidate for a regulatory signal inside cells. Recent evidence suggests, however, that ATPi regulates the behavior of a class of potassium (KATP) channels that are found throughout the cardiovascular system. KATP channels are present in cardiac, skeletal, and vascular smooth muscle. The channels are inhibited by micromolar ATPi, and this inhibition is relieved by micromolar ADPi. We present evidence in support of the idea that variations of ATPi and ADPi, even within normal concentration ranges, may influence cellular function in the heart and vascular system via a direct action on the KATP channel. Furthermore, very specific modulators of KATP channel activity are available. We discuss the mechanism of action of these agents and their interaction with endogenous modulators and consider their potential roles in cardiovascular therapy.
Nichols et al. (Sun,) studied this question.