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

: 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 zP2X3, which shares only 54% identity with closest mammalian P2X subunits. When expressed in Xenopus oocytes in homomeric form, ATP‐gated zP2X3 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 P2X7 receptors, with benzoylbenzoyl ATP (EC50 = 5 μM) ≫ ATP (EC50 = 350 μM) = ADP > α,β‐methylene ATP (EC50 = 480 μM). zP2X3 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. zP2X3 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.