DIADENOSINE 5',5''-P-1,P-5-PENTAPHOSPHATE HARBORS THE PROPERTIES OF ASIGNALING MOLECULE IN THE HEART

Dinucleotide polyphosphates (ApnA) have emerged as signaling molecules in rapidly dividing cells. The presence and role of Ap5A in the heart remain unknown. Here, we report that the myocardium contains abundant amounts of diadenosine 5',5 ''-P-1,P-5-pentaphosphate (Ap5A), a membe r of the ApnA family. Ischemia induced 10-fold decrease in the myocard ial concentration of Ap5A. A target of Ap5A action was identified to b e the cardiac ATP-sensitive K+ (K-ATP) channel, a metabolism-sensitive ion conductance activated in ischemia. At levels found in hearts prio r to ischemia, Ap5A maintained a low probability of K-ATP channel open ing, but at levels found in harts following ischemia, Ap5A allowed a h igh probability of K-ATP channel opening. Taken together, the present data suggest that Ap5A harbors the properties of a signaling molecule involved in the cardiac response to metabolic stress. (C) 1998 Federat ion of European Biochemical Societies.