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 the 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 cardiomyocytes. On a single cardiomyocyte, micromolar ATP induces nonspecific cationic and Cl- currents that depolarize the cells. ATP both increases directly via a G(s) protein and decreases Ca2+ current. ATP activates the inward-rectifying currents (ACh- and ATP-activated K+ currents) and outward K+ currents. P2-purinergic stimulation increases cAMP by activating adenylyl cyclase isoform V. It also involves tyrosine kinases to activate phospholipase C-gamma to produce inositol 1,4,5-trisphosphate acid Cl-/HCO3- exchange to induce a large transient acidosis. No clear correlation is presently possible between an effect: and the activation of a given P2-receptor subtype in cardiomyocytes. ATP itself is generally a positive inotropic agent. Upon rapid application to cells, ATP induces various forms of arrhythmia At the tissue level, arrhythmia could be due to slowing of electrical spread after both Na+ current decrease and cell-to-cell uncoupling as well as cell depolarization and Ca2+ current increase. In as much as the information is available, this review also reports analog effects of UTP and diadenosine polyphosphates.