Extracellular ATP induces fast and transient non-selective cationic currents and cytosolic Ca2+ changes in human umbilical artery smooth muscle cells

Abstract

Ionotropic purinergic receptors (P2X) are expressed in endothelial and smooth muscle cells of blood vessels. ATP acting on smooth muscle P2X receptors is able to induce vasoconstriction in different kind of vessels. However, to our knowledge, there are no reports that directly show the activity of these purinergic receptors in native human vascular smooth muscle cells. In this work, we describe for the first time an ATP-induced current in freshly isolated human umbilical artery (HUA) smooth muscle cells. The current was measured by patch-clamp technique in whole-cell condition on cells clamped at −50 mV. At 100 μM of ATP the current showed a rapid activation and desensitization, and was carried by both Na+ and Ca2+. The current was completely blocked by suramin (300 μM) and partially blocked by 100 μM of Zn2+ without affecting the kinetic of desensitization. All these properties suggest that the ATP-induced ionic currents are mediated through P2X1-like receptors. Moreover, we show that ATP transiently increased cytosolic Ca2+ in “in situ” smooth muscle cells of intact HUA segments and that this response is dependent of extracellular and intracellular Ca2+. These data expand the knowledge of purinergic receptors properties in vascular smooth muscle cells and the probable role of ATP as a paracrine modulator of contractile tone in a human artery which is fundamental for feto-placental blood flow.