Oxygen chemoreceptor inhibition by dopamine D2 receptors in isolated zebrafish gills
Oxygen chemoreceptor inhibition by dopamine D2 receptors in isolated zebrafish gills
Reed, M.; Jonz, M. G.
AbstractDopamine is an essential modulator of oxygen sensing and control of ventilation and was the first neurotransmitter described in the 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 expression was demonstrated in gill neuroepithelial cells (NECs)-analogues of mammalian oxygen chemoreceptors; however, a mechanism for dopamine and D2 in oxygen sensing in the gills had not been defined. The present study tested the hypothesis that presynaptic D2 receptors provide a feedback mechanism that attenuates 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 D2 with dopamine or specific D2 agonist, quinpirole, decreased hypoxic responses in NECs; whereas D2 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. Further, we demonstrate that the response to hypoxia in postsynaptic sensory neurons was dependent upon innervation with NECs, and was subject to modulation by activation of presynaptic D2. 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.