Journal article
Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons
Journal of neurophysiology, Vol.109(3), pp.803-812
02/01/2013
DOI: 10.1152/jn.00460.2012
PMCID: PMC3567397
PMID: 23114210
Abstract
Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by
1
) transient increases in extracellular GABA concentration ([GABA]),
2
) transient postsynaptic depolarization, and
3
) depolarization of presynaptic cells. Transient increases in [GABA] (1 μM) reduced tonic currents; this reduction resulted from GABA-induced shifts in the reversal potential for GABA currents (
E
GABA
). Transient depolarization of postsynaptic neurons reversed the effects of exogenous GABA and potentiated tonic currents. The voltage-dependent potentiation of tonic GABA currents was independent of
E
GABA
shifts and represented postdepolarization potentiation (PDP), an intrinsic GABA
A
receptor property (Ransom CB, Wu Y, Richerson GB.
J Neurosci
30: 7672–7684, 2010). Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect tonic currents. In ConA-treated cells, transient application of 12 mM K
+
to depolarize presynaptic neurons and glia produced a persistent increase in tonic current amplitude. The K
+
-induced increase in tonic current was reversibly inhibited by SKF89976a (40 μM), indicating that this was caused by nonvesicular GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due to GAT1 reversal also occurred in acute hippocampal brain slices. Our results indicate that tonic GABA currents are rapidly regulated by GABA-induced changes in intracellular Cl
−
concentration, PDP of extrasynaptic GABA
A
receptors, and nonvesicular GABA release. These mechanisms may influence tonic inhibition during seizures when neurons are robustly depolarized and extracellular GABA and K
+
concentrations are elevated.
Details
- Title: Subtitle
- Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons
- Creators
- Christopher B Ransom - Epilepsy Center of Excellence, Veterans Affairs Puget Sound Health Care System, Seattle, WashingtonWucheng Tao - Department of Physiology and Biophysics, University of Washington, Seattle, WashingtonYuanming Wu - Department of Neurology, University of Iowa, Iowa City, Iowa; andWilliam J Spain - Epilepsy Center of Excellence, Veterans Affairs Puget Sound Health Care System, Seattle, WashingtonGeorge B Richerson - Department of Neurology, University of Iowa, Iowa City, Iowa; and
- Resource Type
- Journal article
- Publication Details
- Journal of neurophysiology, Vol.109(3), pp.803-812
- DOI
- 10.1152/jn.00460.2012
- PMID
- 23114210
- PMCID
- PMC3567397
- NLM abbreviation
- J Neurophysiol
- ISSN
- 0022-3077
- eISSN
- 1522-1598
- Publisher
- American Physiological Society; Bethesda, MD
- Language
- English
- Date published
- 02/01/2013
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020635802771
Metrics
23 Record Views