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The Journal of Neuroscience, November 19, 2008, 28(47):12510-12522; doi:10.1523/JNEUROSCI.4329-08.2008

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Cellular/Molecular
scn1bb, a Zebrafish Ortholog of SCN1B Expressed in Excitable and Nonexcitable Cells, Affects Motor Neuron Axon Morphology and Touch Sensitivity

Amanda J. Fein,^1 * Melissa A. Wright,^2,3 * Emily A. Slat,¹ Angeles B. Ribera,² and Lori L. Isom¹

¹Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, and ²Department of Physiology and Biophysics, and ³Medical Scientist Training Program, University of Colorado Denver at Anschutz Medical Campus, Aurora, Colorado 80045-6511

Correspondence should be addressed to Lori L. Isom at the above address. Email: lisom{at}umich.edu

Voltage-gated Na⁺ channels initiate and propagate action potentials in excitable cells. Mammalian Na⁺ channels are composed of one pore-forming -subunit and two β-subunits. SCN1B encodes the Na⁺ channel β1-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 β1-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 β1-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.

Key words: Na⁺ channel; auxiliary subunit; cell adhesion; electrophysiology; zebrafish; touch sensitivity

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Received Sept. 10, 2008; revised Oct. 6, 2008; accepted Oct. 9, 2008.

Correspondence should be addressed to Lori L. Isom at the above address. Email: lisom{at}umich.edu

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