Chloride homeostasis differentially affects GABA(A) receptor- and glycine receptor-mediated effects on spontaneous circuit activity in hippocampal cell culture.

Abstract:

:The potassium-chloride cotransporter 2 (KCC2)-dependent intracellular chloride level determines whether neurons respond to GABA and/or glycine by depolarization or hyperpolarization. However, still unknown is the role of KCC2-dependent chloride homeostasis in regulating the spontaneous activity of neuronal circuits via GABA(A) receptor (GABA(A)R) and the glycine receptor (GlyR). In this study, patch-clamp recordings were performed to measure the change of spontaneous neuronal activity in cultured hippocampal neurons. Our results showed that inhibition of KCC2 with furosemide, as well as blockade of GABA(A)R with bicuculline, significantly enhanced circuit activity. Perfusion with bicuculline further enhanced the effects of furosemide on spontaneous circuit activity, while furosemide did not alter the effects of bicuculline. Surprisingly, blockade of GlyR not only induced obvious tonic currents, but also significantly decreased spontaneous synaptic activity. Moreover, inhibition of KCC2 did not change the depressive effect of strychnine on neuronal circuits. Our findings suggest that KCC2-dependent chloride homeostasis is mainly involved in GABA(A)R-mediated synaptic inhibition whereas GlyR-mediated tonic action plays a totally different role in regulating hippocampal circuit activity.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Wang W,Xu TL

doi

10.1016/j.neulet.2006.06.064

subject

Has Abstract

pub_date

2006-10-02 00:00:00

pages

11-6

issue

1-2

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(06)00659-8

journal_volume

406

pub_type

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