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Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel

Item Type:Article
Title:Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel
Creators Name:Staley, K. and Smith, R. and Schaack, J. and Wilcox, C. and Jentsch, T.J.
Abstract:The effect of GABAA receptor activation varies from inhibition to excitation depending on the state of the transmembrane anionic concentration gradient (delta anion). delta anion was genetically altered in cultured dorsal root ganglion neurons via adenoviral vector-mediated expression of ClC-2, a Cl- channel postulated to regulate the Cl- concentration in neurons in which GABAA receptor activation is predominantly inhibitory. ClC-2 expression was verified by the presence of the appropriate mRNA, protein, and membrane conductance. CIC-2 expression resulted in a large negative shift in the Cl- equilibrium potential (ECl) that attenuated the GABA-mediated membrane depolarization and prevented GABAA receptor-mediated action potentials. These results establish that gene transfer of transmembrane ion channels to neurons can be used to demonstrate their physiological function, and that delta anion can be genetically manipulated to alter the function of neuronal GABAA receptors in situ.
Keywords:Adenoviridae, Cultured Cells, Chloride Channels, Electrophysiology, Spinal Ganglia, Gene Expression, Genetic Vectors, Nerve Tissue Proteins, Neurons, GABA-A Receptors, Animals, Rats
Publisher:Cell Press
Page Range:543-551
Date:September 1996
Official Publication:https://doi.org/10.1016/S0896-6273(00)80186-5
PubMed:View item in PubMed

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