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Publication : Novel voltage-dependent Cl(-) channels in striatal medium spiny neurons are unrelated to ClC-1 or other known Ca(2+)-induced Cl(-) channel/transporter types.

First Author  Yarotskyy V Year  2025
Journal  Neurosci Lett Volume  844
Pages  138032 PubMed ID  39491780
Mgi Jnum  J:358466 Mgi Id  MGI:7781273
Doi  10.1016/j.neulet.2024.138032 Citation  Yarotskyy V, et al. (2024) Novel voltage-dependent Cl(-) channels in striatal medium spiny neurons are unrelated to ClC-1 or other known Ca(2+)-induced Cl(-) channel/transporter types. Neurosci Lett 844:138032
abstractText  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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