Identification and characterization of sodium ion channel beta1-like subunits from zebrafish.
Fein, Amanda J.
2007
Abstract
Voltage gated Na<super>+</super> channels are critical for action potential generation and propagation in excitable cells. Na<super>+</super> channels are composed of a pore forming alpha subunit and one or more accessory beta subunits. Mammalian beta subunits increase channel cell surface expression, modulate the voltage dependence of Na<super>+</super> current, accelerate the rate of channel recovery from inactivation, and function as cell adhesion molecules (CAMs). This thesis reports the cloning of three beta1 (<italic> SCN1B</italic>) orthologs from zebrafish. The first ortholog, <italic>scn1ba </italic>, is expressed as two splice variants, Scn1ba_tv1 and Scn1ba_tv2. Both subunits are expressed in brain, retina, skeletal muscle, olfactory pits, and the lateral line system. However, only Scn1b_tv1 is expressed in optic nerve. Scn1ba_tv1 contains a conserved C-terminal tyrosine that corresponds to tyrosine 181 in mammalian Scn1b, which dictates subunit localization in cardiac myocytes. We predict that localization differences in the two <italic> scn1ba</italic> variants result from the presence/absence of this tyrosine. Both variants of <italic>scn1ba</italic> modulate Na<super>+</super> current, thus, we predict that they are functionally homologous to <italic>Scn1b in vivo</italic>. The second ortholog, <italic>scn1bb</italic>, is primarily expressed in non-excitable cell types that are not predicted to express pore-forming a subunits. Scn1bb is expressed in glia in the brain, optic nerve, and spinal cord. It is also expressed in supporting cells in lateral line neuromasts and the olfactory system, and in epithelial cells in the inner ear and lining the pronephric duct. Even though Scn1bb and the pore-forming alpha subunits do not have overlapping expression patterns <italic>in vivo</italic>, Scn1bb retains the ability to modulate Na<super>+</super> currents <italic>in vitro </italic>. We predict that Scn1bb functions primarily as a CAM <italic>in vivo</italic>. <italic>scn1ba2</italic> is the third ortholog identified in this study, and its localization is unknown to date. <italic>scn1ba2</italic> modulates Na<super>+</super> current when expressed in a heterologous system. In contrast to all of the other beta subunits identified, <italic>scn1ba2 </italic> does not produce hyperpolarizing shifts in the voltage dependence of current inactivation, suggesting that its <italic>in vivo</italic> function may be significantly different from the other orthologs identified. With the identification of <italic>SCN1B</italic> orthologs, we are now poised to study the physiological function of beta1-like subunits in zebrafish.Subjects
Beta1 Subunits Cell Adhesion Molecules Channel Characterization Identification Like Na Sodium Ion Channels Voltage-gated Sodium Channels Zebrafish
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