Diadenosine 5',5"-P1,P5-pentaphosphate harbors the properties of a signaling 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"-P1,P5-pentaphosphate (Ap5A), a member of the ApnA family. Ischemia induced 10-fold decrease in the myocardial concentration of Ap5A. A target of Ap5A action was identified to be the cardiac ATP-sensitive K+ (K(ATP)) channel, a metabolism-sensitive ion conductance activated in ischemia. At levels found in hearts prior to ischemia, Ap5A maintained a low probability of K(ATP) channel opening, but at levels found in hearts following ischemia, Ap5A allowed a high 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.
Jovanovic
A
A
Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Jovanovic
S
S
Mays
D C
DC
Lipsky
J J
JJ
Terzic
A
A
D000818:Animals; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000737:chemistry; D007511:Ischemia / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D016276:Ventricular Function
D015226:Dinucleoside Phosphates; D015221:Potassium Channels; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate