Sequence variations at I260 and A1731 contribute to persistent currents in Drosophila sodium channels.
Sequence variations at I260 and A1731 contribute to persistent currents in Drosophila sodium channels.
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I260 和 A1731 的序列变化导致果蝇钠通道中的持续电流
DOI：
10.1016/j.neuroscience.2014.03.028
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发表时间：
2014-05-30
期刊：
影响因子：
3.3
通讯作者：
Dong K
中科院分区：
文献类型：
--
作者：
Gao R;Du Y;Wang L;Nomura Y;Satar G;Gordon D;Gurevitz M;Goldin AL;Dong K
河豚毒素敏感的持续性钠电流，INaP，在阈下电压激活，已在许多脊椎动物和无脊椎动物神经元中检测到。这些电流被认为是调节神经元兴奋性的关键。然而，INaP的分子机制是有争议的。在这项研究中，我们在非洲爪蟾卵母细胞中表达的果蝇钠通道变体中鉴定了具有宽范围电压依赖性的INaP，从-60 mV到20 mV。突变分析揭示了两个变体特异性氨基酸变化，结构域I的S4-S5接头中的I260 T（ILS 4-S5）和结构域IV的电压传感器S4中的A1731 V（IVS 4），有助于INaP。I260 T对超极化电位下的INaP部分至关重要。T260介导的INaP可能是在激活和失活曲线重叠的电压范围内流动的窗口电流的结果。A1731 V负责受损的失活，并有助于在去极化电位的INaP的部分。此外，A1731 V引起两个位点3毒素的活性增强，这两个位点3毒素通过抑制IVS 4的向外运动而诱导持续电流，表明A1731 V抑制IVS 4的向外运动。这些结果为INaP的产生提供了不同机制的分子证据：T260通过增强窗口电流促进INaP，而V1731可能通过抑制IVS 4的向外运动来削弱快速失活。
Tetrodotoxin-sensitive persistent sodium currents, INaP, that activate at subthreshold voltages, have been detected in numerous vertebrate and invertebrate neurons. These currents are believed to be critical for regulating neuronal excitability. However, the molecular mechanism underlying INaP is controversial. In this study, we identified an INaP with a broad range of voltage dependence, from −60 mV to 20 mV, in a Drosophila sodium channel variant expressed in Xenopus oocytes. Mutational analysis revealed that two variant-specific amino acid changes, I260T in the S4–S5 linker of domain I (ILS4–S5) and A1731V in the voltage sensor S4 of domain IV (IVS4), contribute to the INaP. I260T is critical for the portion of INaP at hyperpolarized potentials. The T260-mediated INaP is likely the result of window currents flowing in the voltage range where the activation and inactivation curves overlap. A1731V is responsible for impaired inactivation and contributes to the portion of INaP at depolarized potentials. Furthermore, A1731V causes enhanced activity of two site-3 toxins which induce persistent currents by inhibiting the outward movement of IVS4, suggesting that A1731V inhibits the outward movement of IVS4. These results provided molecular evidence for the involvement of distinct mechanisms in the generation of INaP: T260 contributes to INaP via enhancement of the window current, whereas V1731 impairs fast inactivation probably by inhibiting the outward movement of IVS4.
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影响因子：
16.2
作者：
CHAHINE, M;GEORGE, AL;HORN, R
通讯作者：
HORN, R
DOI：
10.1085/jgp.110.4.391
发表时间：
1997-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Kontis KJ;Rounaghi A;Goldin AL
通讯作者：
Goldin AL
影响因子：
4.8
作者：
Gur, Maya;Kahn, Roy;Gurevitz, Michael
通讯作者：
Gurevitz, Michael
影响因子：
2.5
作者：
Lin, Wei-Hsiang;Wright, Duncan E.;Baines, Richard A.
通讯作者：
Baines, Richard A.
影响因子：
2.8
作者：
Hanck, Dorothy A.;Sheets, Michael F.
通讯作者：
Sheets, Michael F.