Cell type-specific differences in chloride-regulatory mechanisms and GABAA receptor-mediated inhibition in rat substantia nigra

Alexandra Gulácsi, Christian R. Lee, Attila Sík, Tero Viitanen, Kai Kaila, James M. Tepper, T. Freund

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Abstract

The regulation of intracellular chloride has important roles in neuronal function, especially by setting the magnitude and direction of the Cl - flux gated by GABAA receptors. Previous studies have shown that GABAA-mediated inhibition is less effective in dopaminergic than in GABAergic neurons in substantia nigra. We studied whether this phenomenon may be related to a difference in Cl-regulatory mechanisms. Light-microscopic immunocytochemistry revealed that the potassium-chloride cotransporter 2 (KCC2) was localized only in the dendrites of nondopaminergic (primarily GABAergic) neurons in the substantia nigra, whereas the voltage-sensitive chloride channel 2 (ClC-2) was observed only in the dopaminergic neurons of the pars compacta. Electron-microscopic immunogold labeling confirmed that KCC2 is localized in the dendritic plasma membrane of GABAergic neurons close to inhibitory synapses. Confocal microscopy showed that ClC-2 was selectively expressed in the somatic and dendritic cell membranes of the dopaminergic neurons. Gramicidin-perforated-patch recordings revealed that the GABAA IPSP reversal potential was significantly less negative and had a much smaller hyperpolarizing driving force in dopaminergic than in GABAergic neurons. The GABAA reversal potential was significantly less negative in bicarbonate-free buffer in dopaminergic but not in GABAergic neurons. The present study suggests that KCC2 is responsible for maintaining the low intracellular Cl- concentration in nigral GABAergic neurons, whereas a sodium-dependent anion (Cl--HCO3-) exchanger and ClC-2 are likely to serve this role in dopaminergic neurons. The relatively low efficacy of GABAA-mediated inhibition in nigral dopaminergic neurons compared with nigral GABAergic neurons may be related to their lack of KCC2.

Original languageEnglish
Pages (from-to)8237-8246
Number of pages10
JournalJournal of Neuroscience
Volume23
Issue number23
Publication statusPublished - Sep 10 2003

Fingerprint

GABAergic Neurons
Substantia Nigra
GABA-A Receptors
Chlorides
Dopaminergic Neurons
Chloride Channels
Chloride-Bicarbonate Antiporters
Cell Membrane
Gramicidin
Inhibitory Postsynaptic Potentials
Bicarbonates
Dendrites
Confocal Microscopy
Synapses
Dendritic Cells
Anions
Buffers
Sodium
Immunohistochemistry
Electrons

Keywords

  • Chloride channels
  • Chloride regulation
  • Dopaminergic neurons
  • GABAergic neurons
  • Potassium-chloride cotransporters
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cell type-specific differences in chloride-regulatory mechanisms and GABAA receptor-mediated inhibition in rat substantia nigra. / Gulácsi, Alexandra; Lee, Christian R.; Sík, Attila; Viitanen, Tero; Kaila, Kai; Tepper, James M.; Freund, T.

In: Journal of Neuroscience, Vol. 23, No. 23, 10.09.2003, p. 8237-8246.

Research output: Contribution to journalArticle

Gulácsi, A, Lee, CR, Sík, A, Viitanen, T, Kaila, K, Tepper, JM & Freund, T 2003, 'Cell type-specific differences in chloride-regulatory mechanisms and GABAA receptor-mediated inhibition in rat substantia nigra', Journal of Neuroscience, vol. 23, no. 23, pp. 8237-8246.
Gulácsi, Alexandra ; Lee, Christian R. ; Sík, Attila ; Viitanen, Tero ; Kaila, Kai ; Tepper, James M. ; Freund, T. / Cell type-specific differences in chloride-regulatory mechanisms and GABAA receptor-mediated inhibition in rat substantia nigra. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 23. pp. 8237-8246.
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