期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 47, 页码 12510-12522出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4329-08.2008
关键词
Na+ channel; auxiliary subunit; cell adhesion; electrophysiology; zebrafish; touch sensitivity
资金
- National Institutes of Health [MH059980, NS51747, F31 NS047901, F30 NS061409, T32 GM008497, NS038937, NS048154, 5T32 GM007767]
- University of Michigan
Voltage-gated Na+ channels initiate and propagate action potentials in excitable cells. Mammalian Na+ channels are composed of one pore-forming alpha-subunit and two beta-subunits. SCN1B encodes the Na+ channel beta 1-subunit that modulates channel gating and voltage dependence, regulates channel cell surface expression, and functions as a cell adhesion molecule ( CAM). We recently identified scn1ba, a zebrafish ortholog of SCN1B. Here we report that zebrafish express a second beta 1-like paralog, scn1bb. In contrast to the restricted expression of scn1ba mRNA in excitable cells, we detected scn1bb transcripts and protein in several ectodermal derivatives including neurons, glia, the lateral line, peripheral sensory structures, and tissues derived from other germ layers such as the pronephros. As expected for beta 1-subunits, elimination of Scn1bb protein in vivo by morpholino knock-down reduced Na+ current amplitudes in Rohon-Beard neurons of zebrafish embryos, consistent with effects observed in heterologous systems. Further, after Scn1bb knock-down, zebrafish embryos displayed defects in Rohon-Beard mediated touch sensitivity, demonstrating the significance of Scn1bb modulation of Na+ current to organismal behavior. In addition to effects associated with Na+ current modulation, Scn1bb knockdown produced phenotypes consistent with CAM functions. In particular, morpholino knock-down led to abnormal development of ventrally projecting spinal neuron axons, defasciculation of the olfactory nerve, and increased hair cell number in the inner ear. We propose that, in addition to modulation of electrical excitability, Scn1bb plays critical developmental roles by functioning as a CAM in the zebrafish embryonic nervous system.
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