An intracellular motif of P2X(3) receptors is required for functional cross-talk with GABA(A) receptors in nociceptive DRG neurons.
J Neurochem. 2007-08-01; 102(4): 1357-1368
DOI: 10.1111/j.1471-4159.2007.04640.x
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Functional cross-talk between structurally unrelated P2X ATP receptors and
members of the ‘cys-loop’ receptor-channel superfamily represents a
recently-discovered mechanism for rapid modulation of information processing. The
extent and the mechanism of the inhibitory cross-talks between these two classes
of ionotropic receptors remain poorly understood, however. Both ionic and
molecular coupling were proposed to explain cross-inhibition between P2X subtypes
and GABA(A) receptors, suggesting a P2X subunit-dependent mechanism. We show here
that cross-inhibition between neuronal P2X(3) or P2X(2+3) and GABA(A) receptors
does not depend on chloride and calcium ions. We identified an intracellular
QST(386-388) motif in P2X(3) subunits which is required for the functional
coupling with GABA(A) receptors. Moreover the cross-inhibition between native
P2X(3) and GABA receptors in cultured rat dorsal root ganglia (DRG) neurons is
abolished by infusion of a peptide containing the QST motif as well as by viral
expression of the main intracellular loop of GABA(A)beta3 subunits. We provide
evidence that P2X(3) and GABA(A) receptors are colocalized in the soma and
central processes of nociceptive DRG neurons, suggesting that specific
intracellular P2X(3)-GABA(A) subunit interactions underlie a pre-synaptic
cross-talk that might contribute to the regulation of sensory synaptic
transmission in the spinal cord.