Adenosine 5 '-triphosphate: a P2-Purinergic agonist in the myocardium

ATP, besides an intracellular energy source, is an agonist when applied to a variety of different cells including cardiomyocytes. Sources of ATP in th e extracellular milieu are multiple. Extracellular ATP is rapidly degraded by ectonucleotidases. Today ionotropic P2X(1-7) receptors and metabotropic P2Y(1,2,4,6,11) receptors have been cloned and their mRNA found in cardiomy ocytes. On a single cardiomyocyte, micromolar ATP induces nonspecific catio nic and Cl- currents that depolarize the cells. ATP both increases directly via a G(s) protein and decreases Ca2+ current. ATP activates the inward-re ctifying currents (ACh- and ATP-activated K+ currents) and outward K+ curre nts. P2-purinergic stimulation increases cAMP by activating adenylyl cyclas e isoform V. It also involves tyrosine kinases to activate phospholipase C- gamma to produce inositol 1,4,5-trisphosphate acid Cl-/HCO3- exchange to in duce a large transient acidosis. No clear correlation is presently possible between an effect: and the activation of a given P2-receptor subtype in ca rdiomyocytes. ATP itself is generally a positive inotropic agent. Upon rapi d application to cells, ATP induces various forms of arrhythmia At the tiss ue level, arrhythmia could be due to slowing of electrical spread after bot h Na+ current decrease and cell-to-cell uncoupling as well as cell depolari zation and Ca2+ current increase. In as much as the information is availabl e, this review also reports analog effects of UTP and diadenosine polyphosp hates.