Unique functional properties of a sensory neuronal P2X ATP-gated channel from zebrafish

We report here the structural and functional characterization of an ionotro pic P2X ATP receptor from the lower vertebrate zebrafish (Danio rerio). The full-length cDNA encodes a 410-amino acid-long channel subunit zP2X(3), wh ich shares only 54% identity with closest mammalian P2X subunits, When expr essed in Xenopus oocytes in homomeric form, ATP-gated zP2X(3) channels evok ed a unique nonselective cationic current with faster rise time, faster kin etics of desensitization, and slower recovery than any other known P2X chan nel. Interestingly, the order of agonist potency for this P2X receptor was found similar to that of distantly related P2X, receptors, with benzoylbenz oyl ATP (EC50 = 5 mu M) much greater than ATP (EC50 = 350 mu M) = ADP > alp ha,beta-methylene ATP (EC50 = 480 mu M). zP2X(3) receptors are highly sensi tive to blockade by the antagonist trinitrophenyl ATP (IC50 < 5 nM) but are weakly sensitive to the noncompetitive antagonist pyridoxal phosphate-6-az ophenyl-2',4'-disulfonic acid. zP2X(3) subunit mRNA is exclusively expresse d at high levels in trigeminal neurons and Rohon-Beard cells during embryon ic development, suggesting that neuronal P2X receptors mediating fast ATP r esponses were selected early in the vertebrate phylogeny to play an importa nt role in sensory pathways.