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VOL. 73 (4), 1127-1157, 2007 PHYSIOLOGICAL ROLE OF EXTRACELLULAR...

The properties and functional characterization of homomeric and
heteromeric receptors built with the P2X subunits was carried out
by a broad number of scientific groups, and will still require
extensive experimental work (19-25). Recently the P2X7 receptor has
deserved a special attention, not only due to the existence of
polymorphisms and the pronostic of chronic myeloid leukaemia
(CML) in humans and immune system functions, but also due to
recent data of a possible role in other aspects of neuronal functioning
(26-28). For this reason, P2X7 has become a preferential target for
pharmaceutical enterprises (29).

From an electrophysiological point of view, all P2X receptors are
cation selective ligand gated ion channels, with permeability similar
for Na+ and K+, but very high for Ca2+, depending on the implicated
subunits. It is probable that an excess intake of calcium through
these receptors could contribute in vivo to pathologies associated
with P2X receptors (25, 30-36). P2X subunits are formed by two
transmembrane domains with intracellular N and C termini and a
large extracellular ligand binding loop connecting them (Figure 2).
Functional receptors require the assembling of at least three subunits
to form homomeric or heteromeric receptors. It was generally
accepted that P2X7 exclusively formed homomeric receptors,
although recent data points to a coasembling almost with PX4 (37).
The main physiological agonist of functional P2X receptors is ATP,
and for the moment there is a limited battery of nucleotide synthetic
agonists to pharmacologically identify each one of the homomeric or
heteromeric P2X combinations. The same situation occurs with the
antagonist’s disponibility, as it can be seen in Table 2. In spite of
this situation, combination of diverse nucleotide agonists and
antagonists, together with the kinetic behaviour exhibiting or not
desensitization allows the identification of different P2X functional
receptors. Molecular biology and immunohistochemical techniques
are relevant tools to confirm the tissular and cellular location of the
P2X receptor subunits.

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