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ATP and its ionotropic P2X receptors are components of the most ancient signaling system. However, little is known about the distribution and function of purinergic transmission in invertebrates. Here, we cloned, expressed, and pharmacologically characterized the P2X receptors in the sea slug  Aplysia californica —a prominent neuroscience model.  Ac P2X receptors were successfully expressed in  Xenopus  oocytes and displayed activation by ATP with two-phased kinetics and Na + -dependence. Pharmacologically, they were different from other P2X receptors. The ATP analog, Bz-ATP, was a less effective agonist than ATP, and PPADS was a more potent inhibitor of the  Ac P2X receptors than the suramin.  Ac P2X were uniquely expressed within the cerebral F-cluster, the multifunctional integrative neurosecretory center.  Ac P2X receptors were also detected in the chemosensory structures and the early cleavage stages. Therefore, in molluscs, rapid ATP-dependent signaling can be implicated both in development and diverse homeostatic functions. Furthermore, this study illuminates novel cellular and systemic features of P2X-type ligand-gated ion channels for deciphering the evolution of neurotransmitters.

ATP signaling in the integrative neural center of Aplysia californica