Oxygen chemoreceptor inhibition by dopamine D2 receptors in isolated zebrafish gills

• Published in: The Journal of physiology Vol. 603; no. 8; pp. 2369 - 2385
• Main Authors: Reed, Maddison, Jonz, Michael G.
• Format: Journal Article
• Language: English
• Published: London Wiley Subscription Services, Inc 15.04.2025; John Wiley and Sons Inc
• Subjects: Adenylate cyclase; calcium; Calcium (intracellular); Calcium imaging; Carotid body; chemoreceptor; Chemoreceptors (internal); Danio rerio; Dopamine; Dopamine D2 receptors; Forskolin; Gills; Hypoxia; Innervation; Intracellular; NEC; neuroepithelial cell; Neurons; Neuroscience; Neurotransmission; Oxygen; Quinpirole; Sensory neurons; Ventilatory behavior; zebrafish
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/JP287824

Dopamine is an essential modulator of oxygen sensing and control of ventilation and is the most well described and abundant neurotransmitter in the mammalian carotid body. Little is known of the evolutionary significance of dopamine in oxygen sensing, or whether it plays a similar role in anamniotes. In the model vertebrate, zebrafish (Danio rerio), presynaptic dopamine D2 receptor (D2R) expression was demonstrated in gill neuroepithelial cells (NECs), analogues of mammalian oxygen chemoreceptors; however, a mechanism for dopamine and D2R in the gills had not been defined. The present study tested the hypothesis that presynaptic D2Rs provide a feedback mechanism attenuating the chemoreceptor response to hypoxia. Using an isolated gill preparation from Tg(elavl3:GCaMP6s) zebrafish, we measured hypoxia‐induced changes in intracellular Ca2+ concentration ([Ca2+]i) in NECs and postsynaptic neurons. Activation of D2R with dopamine or specific D2R agonist, quinpirole, decreased hypoxic responses in NECs; whereas D2R antagonist, domperidone, had the opposite effect. Addition of SQ22536, an adenylyl cyclase (AC) inhibitor, decreased the effect of hypoxia on [Ca2+]i, similar to dopamine. Activation of AC by forskolin partially recovered the suppressive effect of dopamine on the Ca2+ response to hypoxia. Furthermore, we demonstrate that the response to hypoxia in postsynaptic neurons was dependent upon innervation with NECs, and was subject to modulation by activation of presynaptic D2R. Our results provide the first evidence of neurotransmission of the hypoxic signal at the NEC‐nerve synapse in the gill and suggest that a presynaptic, modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution. Key points For the first time, we present an experimental model that permits imaging of intracellular Ca2+ in identified oxygen chemoreceptors in zebrafish using GCaMP in a whole/intact sensing organ. The hypoxic response of zebrafish chemoreceptors is attenuated by dopamine through a mechanism involving D2 receptors and adenylyl cyclase. Zebrafish oxygen chemoreceptors send a hypoxic signal to postsynaptic (sensory) neurons. Postsynaptic neuronal responses to hypoxia are modulated by presynaptic D2 receptors, suggesting a link between chemoreceptor inhibition by dopamine and modulation of the hypoxic ventilatory response. Our results suggests that a modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution. figure legend Transgenic Tg(elavl3:GCaMP6s) zebrafish, which express an endogenous calcium reporter in gill oxygen chemoreceptors and nerve terminals, were used to explore the role of dopamine in hypoxia signalling. We discovered that dopamine via presynaptic dopamine D2 receptors (D2R) provides a feedback mechanism attenuating the chemoreceptor response to hypoxia.