Domains of P2X receptors involved in desensitization.
ATP-gated ion channels (P2X receptors) are abundantly expressed in both neuronal and nonneuronal tissues, where they can serve as postsynaptic receptors. The response to ATP shows marked desensitization in some tissues but not others. Currents induced by ATP in Xenopus oocytes expressing cloned P2X1 (or P2X3) receptor had strong desensitization, whereas currents in cells expressing P2X2 receptors desensitized relatively little (90% vs. 14% decline of current in a 10-s application). In chimeric receptors, substitution into the P2X1 receptor of either one of two 34-residue segments from the P2X2 receptor removed the desensitization; these segments included the first or the second hydrophobic domain. In contrast, desensitization was introduced into the P2X2 receptor only by providing both these segments of the P2X1 (or P2X3) receptor. This suggests that desensitization requires interaction between the two hydrophobic domains of the receptor, and supports the view that these are membrane-spanning segments.
Werner
P
P
Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, Switzerland.
Seward
E P
EP
Buell
G N
GN
North
R A
RA
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000502:physiology; D017931:DNA Primers; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007473:Ion Channels / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D008961:Models, Structural; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D011983:Receptors, Purinergic / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014981:Xenopus
D017931:DNA Primers; D007473:Ion Channels; D011983:Receptors, Purinergic; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate