Neuroepithelial oxygen chemoreceptors of the zebrafish gill

In aquatic vertebrates, hypoxia induces physiological changes that arise principally from O 2 chemoreceptors of the gill. Neuroepithelial cells (NECs) of the zebrafish gill are morphologically similar to mammalian O 2 chemoreceptors (e.g. carotid body), suggesting that they may play a role in initiating the hypoxia response in fish. We describe morphological changes of zebrafish gill NECs following in vivo exposure to chronic hypoxia, and characterize the cellular mechanisms of O 2 sensing in isolated NECs using patch-clamp electrophysiology. Confocal immunofluorescence studies indicated that chronic hypoxia ( P O 2 = 35 mmHg, 60 days) induced hypertrophy, proliferation and process extension in NECs immunoreactive for serotonin or synaptic vesicle protein (SV2). Under voltage clamp, NECs responded to hypoxia ( P O 2 = 25–140 mmHg) with a dose-dependent decrease in K + current. The current–voltage relationship of the O 2 -sensitive current ( I KO 2 ) reversed near E K and displayed open rectification. Pharmacological characterization indicated that I KO 2 was resistant to 20 m m tetraethylammonium (TEA) and 5 m m 4-aminopyridine (4-AP), but was sensitive to 1 m m quinidine. In current-clamp recordings, hypoxia produced membrane depolarization associated with a conductance decrease; this depolarization was blocked by quinidine, but was insensitive to TEA and 4-AP. These biophysical and pharmacological characteristics suggest that hypoxia sensing in zebrafish gill NECs is mediated by inhibition of a background K + conductance, which generates a receptor potential necessary for neurosecretion and activation of sensory pathways in the gill. This appears to be a fundamental mechanism of O 2 sensing that arose early in vertebrate evolution, and was adopted later in mammalian O 2 chemoreceptors.