Ionic permeability of, and divalent cation effects on, two ATP‐gated cation channels (P2X receptors) expressed in mammalian cells.

Abstract

1. Complementary DNAs for the ATP-gated ion channel subunits P2X, (from human bladder) and P2X2 (from rat phaeochromocytoma (PC12) cells) were used to express the receptors in human embryonic kidney cells by stable transfection, and in Chinese hamster ovary cells by viral infection. 2. Membrane currents evoked by ATP were recorded by the whole-cell patch clamp method.The reversal potential of the current was measured with various intracellular and extracellular solutions and used to compute the relative permeability of the P2X receptor channels. 3. There was no difference between the two receptors with respect to their permeability to monovalent organic cations. The relative permeabilities (Px/PNa) were 2-3, 1P0, 1 0, 0 95, 0'72, 0 5, 0-29, 0-16, 0 04 and 0 03 for guanidinium, potassium, sodium, methylamine, caesium, dimethylamine, 2-methylethanolamine, tris(hydroxymethyl)-aminomethane, tetraethylammonium and N-methyl-D-glucamine, respectively (values for P2X2 receptor). 4. The calcium permeability of P2X1 receptors was greater than that of P2X2 receptors. Under biionic conditions (112 mm calcium outside, 154 mm sodium inside), Pca/PNa values were 3 9 and 2 2, respectively (corrected for ionic activities). 5. ATP-evoked currents in cells expressing the P2X2 receptor were strongly inhibited when the extracellular calcium concentration was increased (0 3-30 mM); the action of ATP could be restored by increasing the ATP concentration. ATP-evoked currents in cells expressing the P2X1 receptor were not inhibited by such increases in the extracellular calcium concentration.

Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1

“…Tolerance to mutagenesis and coordination of Cd 2 + at this site are signs that the P2X receptor has a wider pore than ASIC1. This also agrees with P2X receptor permeation by large organic cations, including guanidinium 15 .…”

Purinergic P2X receptors facilitate inhibitory GABAergic and glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

“…The P2X receptor mediated increase in inhibitory glycinergic and GABAergic neurotransmission observed in this study may serve a vital role in the initial tachycardia, whereas a decrease in the purinergic facilitation of inhibitory neurotransmission, coupled with recruitment of an excitatory neurotransmission to CVNs is likely involved in the protective slowing of the heart (Griffioen et al, 2007a;Griffioen et al, 2007b). P2X receptors are permeable to small cations such as sodium and potassium and have varying permeability to calcium (Evans et al, 1996). Both direct calcium entry through P2X receptors as well as activation of voltage gated calcium channels can facilitate neurotransmission to P2X receptors (Griffioen et al, 2007a).…”

The role of P2X7 receptors in tissue fibrosis: a brief review

“…ATP signaling is mediated by the family of P2 purinergic receptors (P2Rs), divided into metabotropic P2Y receptors and ionotropic P2X receptors [10]. The metabotropic class are G protein-coupled receptors (GPCRs) that initiate signal transduction coupled to a second messenger; the ionotropic class are cationic ligand-operated channels that upon ATP binding open the pore permeable to Na + , K + , and Ca ++ [11,12]. Currently, eight subtypes of the P2Y family and seven subtypes of the P2X family have been characterized [13].…”