Altered chloride homeostasis decreases the action potential threshold and increases hyperexcitability in hippocampal neurons
Sørensen, Andreas T. LU ; Ledri, Marco LU ; Melis, Miriam LU ; Ledri, Litsa Nikitidou ; Andersson, My LU
and Kokaia, Merab
LU
(2017)
In eNeuro
4(6).
- Abstract
Chloride ions play an important role in controlling excitability of principal neurons in the central nervous system. When neurotransmitter GABA is released from inhibitory interneurons, activated GABA type A (GABAA) receptors on principal neurons become permeable to chloride. Typically, chloride flows through activated GABAA receptors into the neurons causing hyperpolarization or shunting inhibition, and in turn inhibits action potential (AP) generation. However, in situations when intracellular chloride concentration is increased, chloride ions can flow in opposite direction, depolarize neurons, and promote AP generation. It is generally recognized that altered chloride homeostasis per se has no effect on the AP threshold. Here, we... (More)
Chloride ions play an important role in controlling excitability of principal neurons in the central nervous system. When neurotransmitter GABA is released from inhibitory interneurons, activated GABA type A (GABAA) receptors on principal neurons become permeable to chloride. Typically, chloride flows through activated GABAA receptors into the neurons causing hyperpolarization or shunting inhibition, and in turn inhibits action potential (AP) generation. However, in situations when intracellular chloride concentration is increased, chloride ions can flow in opposite direction, depolarize neurons, and promote AP generation. It is generally recognized that altered chloride homeostasis per se has no effect on the AP threshold. Here, we demonstrate that chloride overload of mouse principal CA3 pyramidal neurons not only makes these cells more excitable through GABAA receptor activation but also lowers the AP threshold, further aggravating excitability. This phenomenon has not been described in principal neurons and adds to our understanding of mechanisms regulating neuronal and network excitability, particularly in developing brain and during pathological situations with altered chloride homeostasis. This finding further broadens the spectrum of neuronal plasticity regulated by ionic compositions across the cellular membrane.
(Less)
- author
- Sørensen, Andreas T.
LU
; Ledri, Marco
LU
; Melis, Miriam
LU
; Ledri, Litsa Nikitidou
; Andersson, My
LU
and Kokaia, Merab
LU
- organization
- publishing date
- 2017-11-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Action potential threshold, Chloride, ENpHR3.0, GABA receptors, Halorhodopsin, Optogenetics
- in
- eNeuro
- volume
- 4
- issue
- 6
- article number
- e0172-17.2017
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:29379872
- scopus:85043338822
- ISSN
- 2373-2822
- DOI
- 10.1523/ENEURO.0172-17.2017
- language
- English
- LU publication?
- yes
- id
- 59dca570-ebd8-4c09-b6a1-9c5a2c406876
- date added to LUP
- 2018-03-23 14:12:54
- date last changed
- 2024-04-01 03:10:51
@article{59dca570-ebd8-4c09-b6a1-9c5a2c406876,
abstract = {{<p>Chloride ions play an important role in controlling excitability of principal neurons in the central nervous system. When neurotransmitter GABA is released from inhibitory interneurons, activated GABA type A (GABAA) receptors on principal neurons become permeable to chloride. Typically, chloride flows through activated GABAA receptors into the neurons causing hyperpolarization or shunting inhibition, and in turn inhibits action potential (AP) generation. However, in situations when intracellular chloride concentration is increased, chloride ions can flow in opposite direction, depolarize neurons, and promote AP generation. It is generally recognized that altered chloride homeostasis per se has no effect on the AP threshold. Here, we demonstrate that chloride overload of mouse principal CA3 pyramidal neurons not only makes these cells more excitable through GABAA receptor activation but also lowers the AP threshold, further aggravating excitability. This phenomenon has not been described in principal neurons and adds to our understanding of mechanisms regulating neuronal and network excitability, particularly in developing brain and during pathological situations with altered chloride homeostasis. This finding further broadens the spectrum of neuronal plasticity regulated by ionic compositions across the cellular membrane.</p>}},
author = {{Sørensen, Andreas T. and Ledri, Marco and Melis, Miriam and Ledri, Litsa Nikitidou and Andersson, My and Kokaia, Merab}},
issn = {{2373-2822}},
keywords = {{Action potential threshold; Chloride; ENpHR3.0; GABA receptors; Halorhodopsin; Optogenetics}},
language = {{eng}},
month = {{11}},
number = {{6}},
publisher = {{Society for Neuroscience}},
series = {{eNeuro}},
title = {{Altered chloride homeostasis decreases the action potential threshold and increases hyperexcitability in hippocampal neurons}},
url = {{http://dx.doi.org/10.1523/ENEURO.0172-17.2017}},
doi = {{10.1523/ENEURO.0172-17.2017}},
volume = {{4}},
year = {{2017}},
}