Functional modulation of human brain Nav1.3 sodium channels, expressed in mammalian cells, by auxiliary β1, β2 and β3 subunits
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- 作者：Meadows ; L.S. ; Chen ; Y.H. ; Powell ; A.J. ; Clare ; J.J. ; Ragsdale ; D.S.
- 关键词：voltage-gated sodium channel ; Chinese hamster ovary cell ; voltage cl pain ; CHO ; Chinese hamster ovary ; EGTA ; ethyleneglycolbis(aminoethyl ether)tetra-acetate ; HEK ; human embryonic kidney ; HEPES ; N-2-hydroxyethylpiperazine-N&prime ; -2-ethanesulfonic acid ; h
- 刊名：Neuroscience
- 出版年：2002
- 出版时间：October 11, 2002
- 年：2002
- 卷：114
- 期：3
- 页码：745-753
- 全文大小：294 K
文摘
Voltage-gated sodium channels consist of a pore-forming α subunit and two auxiliary β subunits. Excitable cells express multiple α subtypes, designated Nav1.1–Nav1.9, and three β subunits, designated β1, β2 and β3. Understanding how the different α subtypes, in combination with the various β subunits, determine sodium channel behavior is important for elucidating the molecular basis of sodium channel functional diversity. In this study, we used whole-cell electrophysiological recording to examine the properties of the human Nav1.3 α subtype, stably expressed in Chinese hamster ovary cells, and to investigate modulation of Nav1.3 function by β1, β2 and β3 subunits. In the absence of β subunits, human Nav1.3 formed channels that inactivated rapidly (τinactivation
0.5 ms at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using an intracellular solution with aspartate as the main anion, the midpoint for channel activation was 
−12 mV. The midpoint for inactivation, determined using 100-ms conditioning pulses, was −47 mV. The time constant for repriming of inactivated channels at −80 mV was 6 ms. Coexpression of β1 or β3 did not affect inactivation time course or the voltage dependence of activation, but shifted the inactivation curve 10 mV negative, and slowed the repriming rate ca. three-fold. β2 did not affect channel properties, either by itself or in combination with β1 or β3.
0.5 ms at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using an intracellular solution with aspartate as the main anion, the midpoint for channel activation was −12 mV. The midpoint for inactivation, determined using 100-ms conditioning pulses, was −47 mV. The time constant for repriming of inactivated channels at −80 mV was 6 ms. Coexpression of β1 or β3 did not affect inactivation time course or the voltage dependence of activation, but shifted the inactivation curve 10 mV negative, and slowed the repriming rate ca. three-fold. β2 did not affect channel properties, either by itself or in combination with β1 or β3.