Unique Functional Properties of a Sensory Neuronal P2X ATP‐Gated Channel from Zebrafish

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Abstract
We report here the structural and functional characterization of an ionotropic P2X ATP receptor from the lower vertebrate zebrafish (Danio rerio). The full-length cDNA encodes a 410-amino acid-long channel subunit zP2X(3), which shares only 54% identity with closest mammalian P2X subunits, When expressed in Xenopus oocytes in homomeric form, ATP-gated zP2X(3) channels evoked a unique nonselective cationic current with faster rise time, faster kinetics of desensitization, and slower recovery than any other known P2X channel. Interestingly, the order of agonist potency for this P2X receptor was found similar to that of distantly related P2X, receptors, with benzoylbenzoyl ATP (EC50 = 5 mu M) much greater than ATP (EC50 = 350 mu M) = ADP > alpha,beta-methylene ATP (EC50 = 480 mu M). zP2X(3) receptors are highly sensitive to blockade by the antagonist trinitrophenyl ATP (IC50 < 5 nM) but are weakly sensitive to the noncompetitive antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid. zP2X(3) subunit mRNA is exclusively expressed at high levels in trigeminal neurons and Rohon-Beard cells during embryonic development, suggesting that neuronal P2X receptors mediating fast ATP responses were selected early in the vertebrate phylogeny to play an important role in sensory pathways.