A novel cyclic nucleotide-gated ion channel enriched in synaptic terminals of isotocin neurons in zebrafish brain and pituitary

• Published in: Neuroscience Vol. 165; no. 1; pp. 79 - 89
• Main Authors: Khan, S, Perry, C, Tetreault, M.L, Henry, D, Trimmer, J.S, Zimmerman, A.L, Matthews, G
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 13.01.2010; Elsevier
• Subjects: Animals; Antibodies, Monoclonal; Biological and medical sciences; Brain - metabolism; Brain - ultrastructure; Calcium - metabolism; calcium entry; Cell Membrane Permeability; Cross Reactions; cyclic nucleotides; Danio rerio; Female; Freshwater; Fundamental and applied biological sciences. Psychology; Ion Channels - immunology; Ion Channels - metabolism; neuroendocrine cells; neurohypophysis; Neurology; Neurons - metabolism; Neurons - ultrastructure; Oocytes - metabolism; oxytocin; Oxytocin - analogs & derivatives; Oxytocin - metabolism; Pituitary Gland - metabolism; Pituitary Gland - ultrastructure; Presynaptic Terminals - metabolism; synaptic plasticity; Teleostei; Vertebrates: nervous system and sense organs; Xenopus; Zebrafish - metabolism; Zebrafish Proteins - immunology; Zebrafish Proteins - metabolism; CNGA5; PT; ACTH; phosphate-buffered saline; PRL; adrenocorticotropic hormone; preoptic region; synaptic vesicle protein 2 A; C-terminal; N-methyl-D-glucamine; cyclic nucleotides; CNGA1; CNGA2; CNGA3; FSH; hypophysis; tectum opticum; follicle stimulating hormone; PBS; neurohypophysis; somatolactin; oxytocin; neuroendocrine cells; MO; calcium entry; alpha melanocyte stimulating hormone; NMDG; luteinizing hormone; inferior reticular formation; Hy; cyclic nucleotide-gated channels; IRF; intermediate reticular formation; cyclic nucleotide-gated channel alpha subunit 1; CNG channels; cyclic nucleotide-gated channel alpha subunit 3; cyclic nucleotide-gated channel alpha subunit 2; cyclic nucleotide-gated channel alpha subunit 5; oc; T; SV2A; SL; growth hormone; α-MSH; thalamus; TeO; GH; prolactin; GST; optic chiasm; carboxy terminal; glutathione S-transferase; posterior tuberculum; IMRF; synaptic plasticity; LH; medulla oblongata; PO; Calcium; Oxytocin; Central nervous system; Ionic channel; Encephalon; Vertebrata; Brachydanio rerio; Neuron; Pisces; Neurosecretory cell; Synaptic plasticity; Cyclic nucleotide; Pituitary gland; Neurohypophysis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.09.040

Abstract Cyclic nucleotide-gated (CNG) channels are nonselective cation channels opened by binding of intracellular cyclic GMP or cyclic AMP. CNG channels mediate sensory transduction in the rods and cones of the retina and in olfactory sensory neurons, but in addition, CNG channels are also expressed elsewhere in the CNS, where their physiological roles have not yet been well defined. Besides the CNG channel subtypes that mediate vision and olfaction, zebrafish has an additional subtype, CNGA5, which is expressed almost exclusively in the brain. We have generated CNGA5-specific monoclonal antibodies, which we use here to show that immunoreactivity for CNGA5 channels is highly enriched in synaptic terminals of a discrete set of neurons that project to a subregion of the pituitary, as well as diffusely in the brain and spinal cord. Double labeling with a variety of antibodies against pituitary hormones revealed that CNGA5 is located in the terminals of neuroendocrine cells that secrete the nonapeptide hormone/transmitter isotocin in the neurohypophysis, brain, and spinal cord. Furthermore, we show that CNGA5 channels expressed in Xenopus oocytes are highly permeable to Ca2+ , which suggests that the channels are capable of modulating isotocin release in the zebrafish brain and pituitary. Isotocin is the teleost homolog of the mammalian hormone oxytocin, and like oxytocin, it regulates reproductive and social behavior. Therefore, the high calcium permeability of CNGA5 channels and their strategic location in isotocin-secreting synaptic terminals suggest that activation of CNGA5 channels in response to cyclic nucleotide signaling may have wide-ranging neuroendocrine and behavioral effects.