Neuromodulation of calcium current by extracellular ATP in isolated ventricular myocytes

Abstract

The effects of extracellular ATP on the L-type Ca2+ current (I(Ca), action potential, and resting and intracellular Ca2+ levels were examined in enzymatically isolated myocytes from the right ventricles of ferrets. Extracellular ATP decreased the peak amplitude of I(Ca) in a time- and concentration-dependent manner. The concentration-response relationship for ATP inhibition of I(Ca) was well described by a conventional Michaelis- Menten relationship with a half maximal inhibitory concentration of 1 μM and a maximal effect of 50%. Extracellular ATP did not change the resting myoplasmic Ca2+ levels; however, it did decrease the Ca2+ transient. The effects of extracellular ATP were mediated independently of adenosine A1 receptors and a pertussis-toxin sensitive G protein. Pharmacological characterization of receptor subtype using ATP analogs was consistent with ATP binding to a P(2Y) type receptor.