Journal article
Postdepolarization Potentiation of GABAA Receptors: A Novel Mechanism Regulating Tonic Conductance in Hippocampal Neurons
The Journal of neuroscience, Vol.30(22), pp.7672-7684
06/02/2010
DOI: 10.1523/JNEUROSCI.0290-10.2010
PMID: 20519542
Abstract
Ambient GABA in the brain activates GABA
A
receptors to produce tonic inhibition. Membrane potential influences both GABA transport and GABA
A
receptors and could thereby regulate tonic inhibition. We investigated the voltage dependence of tonic currents in cultured rat hippocampal neurons using patch-clamp techniques. Tonic GABA
A
conductance increased with depolarization from 15 ± 3 pS/pF at −80 mV to 29 ± 5 pS/pF at −40 mV. Inhibition of vesicular or nonvesicular GABA release did not prevent voltage-dependent increases of tonic conductance. Currents evoked with exogenous GABA (1 μ
m
) were outwardly rectifying, similar to tonic currents caused by endogenous GABA. These results indicate that the voltage-dependent increase of tonic conductance was attributable to intrinsic GABA
A
receptor properties rather than an elevation of ambient GABA. After transient depolarization to +40 mV, endogenous tonic currents measured at −60 mV were increased by 75 ± 17%. This novel form of tonic current modulation, termed postdepolarization potentiation (PDP), recovered with a time constant of 63 s, was increased by exogenous GABA and inhibited by GABA
A
receptor antagonists. Measurements of
E
GABA
showed PDP was caused by increased conductance and not a change in the anion gradient. To assess the functional significance of PDP, we used voltage-clamp waveforms that replicated epileptiform activity. PDP was produced by this pathophysiological depolarization. These data show that depolarization produces prolonged potentiation of tonic conductance attributable to voltage-dependent properties of GABA
A
receptors. These properties are well suited to limit excitability during pathophysiological depolarization accompanied by rises in ambient GABA, such as occur during seizures and ischemia.
Details
- Title: Subtitle
- Postdepolarization Potentiation of GABAA Receptors: A Novel Mechanism Regulating Tonic Conductance in Hippocampal Neurons
- Creators
- Christopher B Ransom - Departments of Neurology andYuanming Wu - Departments of Neurology andGeorge B Richerson - Departments of Neurology and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.30(22), pp.7672-7684
- DOI
- 10.1523/JNEUROSCI.0290-10.2010
- PMID
- 20519542
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- Society for Neuroscience
- Language
- English
- Date published
- 06/02/2010
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020639302771
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