Molecular cloning, functional characterization and possible cooperativity between the murine P2X4 and P2X4a receptors

Brain Res Mol Brain Res. 1999 Feb 5;64(2):246-54. doi: 10.1016/s0169-328x(98)00328-3.


We have cloned and functionally characterised the mouse orthologue of the P2X4 receptor, mP2X4, and a splice variant of this receptor, mP2X4a. mP2X4 is 388 amino acids in length and shares 94% and 87% identity with the rat and human P2X4 receptors, respectively, while mP2X4a is 361 amino acids in length and lacks a 27-amino acid region in the extracellular domain corresponding to exon 6 of the known P2X receptor gene structures. When expressed in Xenopus laevis oocytes, mP2X4 produces a rapid inward current in response to ATP with an EC50 of 1.68+/-0.2 microM, consistent with the affinity of the rat and human P2X4 receptors for ATP. This agonist response is potentiated by the P2X receptor antagonists suramin, Reactive blue 2 and, over a limited concentration range, by PPADS. Although mP2X4a forms a poorly functional homomeric receptor, it appears able to interact with the full-length mP2X4 subunit to result in a functional channel with a reduced affinity for ATP. These results suggest a possible role for splice variants of P2X receptors in the formation of functional heteromeric ion channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neuropeptides / isolation & purification*
  • Neuropeptides / physiology
  • Oocytes / metabolism
  • Rats
  • Receptors, Purinergic P2 / isolation & purification*
  • Receptors, Purinergic P2 / physiology
  • Xenopus laevis


  • Neuropeptides
  • Receptors, Purinergic P2

Associated data

  • GENBANK/AF089751
  • GENBANK/AF089752