Novel voltage-dependent Cl− channels in striatal medium spiny neurons are unrelated to ClC-1 or other known Ca2+-induced Cl− channel/transporter types

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2024-11-02 DOI:10.1016/j.neulet.2024.138032

Viktor Yarotskyy , Liangru Contois , Yun-Kyung Hahn , Sara R. Nass , Pamela E. Knapp , Kurt F. Hauser

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引用次数: 0

Abstract

Intracellular chloride (Cl⁻) homeostasis is a critical regulator of neuronal excitability. Voltage-dependent neuronal Cl⁻ channels remain the least understood in terms of their role as a source of Cl⁻ entry controlling excitability. We have shown recently that striatal medium spiny neurons (MSNs) express a functional Cl⁻ conducting ClC-1-like channel with properties similar but not identical to native ClC-1 channels (Yarotskyy, V., Lark, A.R.S., Nass S.R., Hahn, Y.K., Marone, M.G., McQuiston, A.R., Knapp, P.E., Hauser, K.F. (2022) Am. J. Physiol. Cell. Physiol. 322 (2022) C395-C409). Using a myotonic SWR/J-Clcn1^adr-mto/J mouse model with a premature stop codon for the ClC-1 channel rendering it non-functional, we demonstrate that striatal MSNs isolated from wild type (wt) and homozygous mutant (adr) mouse embryos have identical voltage-dependent outwardly rectifying Cl⁻ currents. In contrast and as expected, homozygous adr skeletal muscle flexor digitorum brevis (FDB) fibers display nominal macroscopic Cl⁻ currents compared to heterozygous wild-type adr FDB fibers. Together, our findings demonstrate that the novel ClC-1-like channels in MSNs are unrelated to skeletal muscle-specific ClC-1 channels, and therefore represent a unique voltage-dependent neuronal Cl⁻ channel of unknown identity.

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纹状体中刺神经元中的新型电压依赖性 Cl- 通道与 ClC-1 或其他已知的 Ca2+ 诱导的 Cl- 通道/转运体类型无关。

细胞内氯化物（Cl-）平衡是神经元兴奋性的关键调节因子。电压依赖性神经元 Cl- 通道作为控制兴奋性的 Cl- 输入源，人们对其作用的了解仍然最少。我们最近研究发现，纹状体中刺神经元（MSNs）表达一种功能性 Cl- 传导 ClC-1 样通道，其特性与原生 ClC-1 通道相似但不完全相同（Yarotskyy, V., Lark, A.R.S., Nass S.R., Hahn, Y.K., Marone, M.G., McQuiston, A.R., Knapp, P.E., Hauser, K.F. (2022) Am. J. Physiol.J. Physiol.Cell.322 (2022) C395-C409）。我们利用一个肌营养不良的 SWR/J-Clcn1adr-mto/J 小鼠模型（该模型中的 ClC-1 通道因过早终止密码子而失去功能），证明了从野生型（wt）和同基因突变型（adr）小鼠胚胎中分离出的纹状体 MSN 具有相同的电压依赖性外向整流 Cl- 电流。相反，正如所预期的那样，与杂合子野生型 adr FDB 纤维相比，同源突变体骨骼肌屈指肌（FDB）纤维显示出微弱的宏观 Cl- 电流。总之，我们的研究结果表明，MSN 中的新型 ClC-1 样通道与骨骼肌特异性 ClC-1 通道无关，因此代表了一种身份不明的独特的电压依赖性神经元 Cl- 通道。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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