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Vol. 296, Issue 3, 1043-1050, March 2001
Autonomic Neuroscience Institute, Royal Free and University College
Medical School, Royal Free Campus, Hampstead, London, United
Kingdom
Using voltage-clamp procedures on Xenopus oocytes,
agonist-evoked ionic currents by P2X receptors resulting from the
coexpression of P2X2 and P2X3 subunits were
compared against the agonist responses of homomeric P2X2
and P2X3 receptors. With the quantity of P2X3 mRNA kept constant and quantity of P2X2 mRNA progressively
increased, expressed P2X receptors changed from a P2X3-like
receptor to a P2X2-like receptor. In all cases, however,
agonist-evoked responses comprised biphasic (fast and slow)
currents
the former showing the properties of P2X3
receptors and latter consistent with the presence of P2X2
and P2X2/3 receptors. Using desensitization procedures, the
P2X3-like fast current was selectively removed to allow the slow current to be studied in isolation. P2X2/3 receptors
were then characterized by slowly inactivating inward currents that were reproducible within 30 s of washout and whose pharmacological profile [selective agonists, Ap5A >
,
-methylene ATP
,
-methylene ATP > UTP;
antagonists, TNP-ATP
suramin
Reactive blue-2 (RB-2)] contrasted with the profile of P2X2 receptors
(Ap5A,
,
-methylene ATP,
,
-methylene ATP, and
UTP inactive; antagonists, RB-2 > TNP-ATP > suramin). Thus,
our experiments reveal that coexpression of two P2X subunits, which of
themselves can generate functional homomeric receptors, results in a
complex population of heterogeneous P2X receptors
in this case
P2X2, P2X3, and P2X2/3 receptors.
Depending on the relative levels of P2X subunit coexpression, the
operational profile of the resultant P2X receptors can change from one
phenotype to another. This spectrum may explain the variability of
agonist responses in small sensory neurons that also express
P2X2 and P2X3 subunits in different amounts.
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