Work

Contribution of Resting Conductance, GABAA-Receptor Mediated Miniature Synaptic Currents and Neurosteroid to Chloride Homeostasis in Central Neurons

Year: 2017

Type: article

Abstract: Maintenance of a low intraneuronal Cl–concentration, [Cl–]i, is critical for inhibition in the CNS. Here, the contribution of passive, conductive Cl–flux to recovery of [Cl–]iafter a high load was analyzed in mature central neurons from rat. A novel method for quantifying the resting Cl–conductance, important for [Cl–]irecovery, was developed and the possible contribution of GABAAand glycine receptors and of ClC-2 channels to this conductance was analyzed. The hypothesis that spontaneous, action potential-independent release of GABA is important for [Cl–]irecovery was tested. [Cl–]iwas examined by gramicidin-perforated patch recordings in medial preoptic neurons. Cells were loaded with Cl–by combining GABA or glycine application with a depolarized voltage, and the time course of [Cl–]iwas followed by measurements of the Cl–equilibrium potential,as obtained from the current recorded during voltage ramps combined with GABA or glycine application. The results show that passive Cl–flux contributes significantly, in the same order of magnitude as does K+-Cl–cotransporter 2 (KCC2), to [Cl–]irecovery and that Cl–conductance accounts for ∼ 6% of the total resting conductance. A major fraction of this resting Cl–conductance is picrotoxin (PTX)-sensitive and likely due to open GABAAreceptors, but ClC-2 channels do not contribute. The results also show that when the decay of GABAAreceptor-mediated miniature postsynaptic currents (minis) is slowed by the neurosteroid allopregnanolone, such minis may significantly quicken [Cl–]irecovery, suggesting a possible steroid-regulated role for minis in the control of Cl–homeostasis.

Source: eNeuro

DOI: 10.1523/eneuro.0019-17.2017

Authors: Tushar D. Yelhekar, Michael Druzin, Staffan Johansson

Institution: Umeå University

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,925