Extracellular ATP induces Ca2+ transients in cardiac myocytes which are potentiated by norepinephrine.
Isolated rat ventricular cardiac myocytes loaded with the fluorescent calcium indicator fura2 showed significant changes in intracellular calcium concentrations upon exposure to greater than 1 microM ATP (EC50 = 7.4 +/- 1.3 microM, n = 4, SE), suggesting that extracellular ATP may have an important influence on myocardial contractility. The response was found to be highly ATP specific and required extracellular calcium. Furthermore, 30 s pretreatment of the cells with 0.2-1 microM norepinephrine decreased the concentration of ATP required for the Ca2+ transient, shifting the EC50 for ATP to 1.7 +/- 0.1 microM (n = 3, SE). beta-Propranolol (a beta 1-receptor antagonist) prevented potentiation, whereas phentolamine (an alpha 1-receptor antagonist) did not, indicating that regulation is through the beta 1-adrenergic receptor. ATP and norepinephrine released locally from sympathetic neurons may act in concert through the ATP and beta 1-adrenergic receptors to regulate myocardial calcium homeostasis.
De Young
M B
MB
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106.
Scarpa
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D002118:Calcium; D009638:Norepinephrine