Sex-specific KCC2 expression and GABAA receptor function in rat substantia nigra

Aristea S. Galanopoulou, Andreas Kyrozis, Olga I. Claudio, Patric K. Stanton, Solomon L. Moshe

Research output: Contribution to journalArticle

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Abstract

GABAA receptor activation by muscimol has sex and age specific effects on substantia nigra reticulata (SNR)-mediated control of generalized seizures. GABAA receptor agonists depolarize or hyperpolarize neurons depending upon the level of expression of the neuronal specific potassium chloride contransporter KCC2. We studied KCC2 mRNA expression in the SNR as a function of sex and age and correlated KCC2 expression with the in vivo and in vitro effects of muscimol. Methods included in situ hybridization, gramicidin-perforated patch clamp and fura-2 AM imaging of acute SNR slices. KCC2 mRNA expression increased between postnatal days (PN) 15 and 30 in both sexes, and reached adult levels in males by PN30. Female PN15 and PN30 SNR neurons contained more KCC2 mRNA compared with age-matched males. In male PN14-17 rats, bath application of the GABAA receptor agonist muscimol in acute SNR slices depolarized neurons and increased intracellular calcium concentration ([Ca2+]i). Furthermore, acute in vivo administration of muscimol upregulated, whereas blockade of L-type voltage sensitive calcium channels with nifedipine downregulated KCC2 mRNA. In contrast, in female PN14-17 rats, bath application of muscimol hyperpolarized SNR neurons and did not alter [Ca2+]i. In vivo muscimol administration acutely downregulated KCC2 mRNA expression whereas nifedipine had no effect. The lower expression of KCC2 mRNA in infantile male SNR neurons may explain why muscimol-induced depolarization and [Ca2+] i increases occur only in males. Consequently, GABAA receptor activation selectively upregulates the expression of calcium-regulated genes, such as KCC2, in male SNR, promoting the sexual differentiation of the SNR.

Original languageEnglish (US)
Pages (from-to)628-637
Number of pages10
JournalExperimental Neurology
Volume183
Issue number2
DOIs
StatePublished - Oct 1 2003

Fingerprint

Substantia Nigra
GABA-A Receptors
Muscimol
Messenger RNA
Neurons
GABA-A Receptor Agonists
Nifedipine
Baths
Down-Regulation
Calcium
Gramicidin
Pars Reticulata
Sex Differentiation
Potassium Chloride
Fura-2
Calcium Channels
In Situ Hybridization
Seizures
Up-Regulation

Keywords

  • Calcium
  • Epilepsy
  • GABA receptors
  • KCC2
  • Muscimol
  • Nifedipine
  • Potassium-chloride cotransporter
  • Substantia nigra pars reticulata

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Sex-specific KCC2 expression and GABAA receptor function in rat substantia nigra. / Galanopoulou, Aristea S.; Kyrozis, Andreas; Claudio, Olga I.; Stanton, Patric K.; Moshe, Solomon L.

In: Experimental Neurology, Vol. 183, No. 2, 01.10.2003, p. 628-637.

Research output: Contribution to journalArticle

Galanopoulou, Aristea S. ; Kyrozis, Andreas ; Claudio, Olga I. ; Stanton, Patric K. ; Moshe, Solomon L. / Sex-specific KCC2 expression and GABAA receptor function in rat substantia nigra. In: Experimental Neurology. 2003 ; Vol. 183, No. 2. pp. 628-637.
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T1 - Sex-specific KCC2 expression and GABAA receptor function in rat substantia nigra

AU - Galanopoulou, Aristea S.

AU - Kyrozis, Andreas

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AU - Stanton, Patric K.

AU - Moshe, Solomon L.

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