Received for publication September 24, 2007.
Revised September 24, 2007.
Accepted for publication September 25, 2007.

Go It Alone No More - P2X7 Joins the Society of Heteromeric ATP-Gated Ion Channel Receptors (Relates to article by Guo, et al., FastForward 4 Sept 07)

Abstract

P2X receptors (P2XR) function as ATP-gated non-selective ion channels permeable to Na⁺, K⁺, and Ca²⁺ and they are expressed in a wide range of excitable, epithelial/endothelial, and immune effector cell types. The channels are trimeric complexes composed of protein subunits encoded by seven different P2XR genes expressed in mammalian and other vertebrate genomes. Current genetic, biochemical, and/or physiological evidence indicates that the extended family of functional P2X receptors includes six homomeric channels composed of P2X1, P2X2, P2X3, P2X4, P2X5, or P2X7 subunits and six heteromeric channels that involve subunit pairings of P2X1/P2X2, P2X1/P2X4, P2X1/P2X5, P2X2/P2X3, P2X2/P2X6, or P2X4/P2X6. Thus, all P2XR subtypes - with the salient exception of P2X7R - have previously been implicated in the assembly of heteromeric ATP-gated ion channels that can comprise unique pharmacological targets in different tissues. The assumed "go-it alone" function of the P2X7R has important implications because agents that target this particular receptor have been proposed as useful therapeutics in various autoinflammatory diseases or amelioration of inflammatory pain. However, this assumption and the interpretations based on it now require reevaluation in the light of a new report in this issue of Molecular Pharmacology that provides convincing biochemical and electrophysiological evidence for the existence of P2X4/P2X7 heteromeric receptors.

Key words: Purinergic, Purinergic

This article has been cited by other articles:

				D. Donnelly-Roberts, S. McGaraughty, C.-C. Shieh, P. Honore, and M. F. Jarvis Painful Purinergic Receptors J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 409 - 415. [Abstract] [Full Text] [PDF]