Independent and joint modulation of rat Na_v1.6 voltage-gated sodium channels by coexpression with the auxiliary β1 and β2 subunits

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• 作者：Jianguo Tan^a ; David M. Soderlund ; ^a ; ^{dms6@cornell.edu"" rel=""nofollow}
• 关键词：Voltage-gated sodium channels ; Na_v1.6 ; &#x3b2 ; Subunits ; Voltage cl Kinetics ; Steady-state properties
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：22 April 2011
• 年：2011
• 卷：407
• 期：4
• 页码：788-792
• 全文大小：359 K

文摘

The Na_v1.6 voltage-gated sodium channel α subunit isoform is the most abundant isoform in the brain and is implicated in the transmission of high frequency action potentials. Purification and immunocytochemical studies imply that Na_v1.6 exist predominantly as Na_v1.6 + β1 + β2 heterotrimeric complexes. We assessed the independent and joint effects of the rat β1 and β2 subunits on the gating and kinetic properties of rat Na_v1.6 channels by recording whole-cell currents in the two-electrode voltage clamp configuration following transient expression in Xenopus oocytes. The β1 subunit accelerated fast inactivation of sodium currents but had no effect on the voltage dependence of their activation and steady-state inactivation and also prevented the decline of currents following trains of high-frequency depolarizing prepulses. The β2 subunit selectively retarded the fast phase of fast inactivation and shifted the voltage dependence of activation towards depolarization without affecting other gating properties and had no effect on the decline of currents following repeated depolarization. The β1 and β2 subunits expressed together accelerated both kinetic phases of fast inactivation, shifted the voltage dependence of activation towards hyperpolarization, and gave currents with a persistent component typical of those recorded from neurons expressing Na_v1.6 sodium channels. These results identify unique effects of the β1 and β2 subunits and demonstrate that joint modulation by both auxiliary subunits gives channel properties that are not predicted by the effects of individual subunits.