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Vol. 54, Issue 6, 989-993, December 1998
Department of Pharmacological and Physiological Science, Saint
Louis University School of Medicine, St. Louis, Missouri 63104
P2X receptors are a family of ion channels gated by extracellular ATP.
Each member of the family can form functional homomeric channels, but
only P2X2 and P2X3 have been shown to combine
to form a unique heteromeric channel. Data from in situ
hybridization studies suggest that P2X1 and
P2X5 may also co-assemble. In this study, we tested this
hypothesis by expressing recombinant P2X1 and
P2X5 receptor subunits either individually or together in human embryonic kidney 293 cells. In cells expressing the homomeric P2X1 receptor, 30 µM 
,
-methylene ATP
(,-me-ATP) evoked robust currents that completely desensitized in
less than 1 sec, whereas ,-me-ATP failed to evoke current in
cells expressing the homomeric P2X5 receptor. By contrast,
,-me-ATP evoked biphasic currents with a pronounced
nondesensitizing plateau phase in cells that co-expressed both
subunits. Further, the EC50 for ,-me-ATP was greater
in cells expressing both P2X1 and P2X5 than in
cells expressing P2X1 alone (5 and 1.6 µM,
respectively). Heteromeric assembly was confirmed using a
co-immunoprecipitation assay of epitope-tagged P2X1 and
P2X5 subunits. In summary, this study provides biochemical and functional evidence of a novel channel formed by P2X subunit heteropolymerization. This finding suggests that heteromeric subunit assembly constitutes an important mechanism for generating functional diversity of ATP-mediated responses.
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