Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle

John Wade, Kevin Breslin, LJ McDaid, Bronac Flanagan, Jim Harkin, KongFatt Wong-Lin, Alexei Verkhratsky, Steve Hall, Harm Van Zalinge

Research output: Contribution to conferenceAbstract

Abstract

Recent studies have demonstrated that neuronal activity triggers transient increases in the cytosolic [Na+]PsC and [K+]PsC concentrations at the perisynaptic cradle (PsC). These microdomains strongly correlate with several crucial homeostatic pathways including K+ uptake by astrocytes and neuronal metabolic support. The aim of this poster is to present using mathematical modelling, a new hypothesis whereby microdomain formation is a direct result of fixed negatively charged ions associated with the dipole heads of membrane phospholipids. Specifically, we hypothesize that these negatively charged lipids result in deep potential wells near the dipole heads restricting the flow of cations in thin astrocyte processes to “hopping” between wells (well hopping) as they transverse the process. Results show that for very thin astrocyte processes, with a large surface to volume ratio, cation retention in wells dominates over conventional electrochemical diffusion (see Figure below). Essentially this low conductance pathway semi-isolates the PsC from the astrocytic soma allowing microdomains to form at the PsC. This has implications for K+ clearance as [K+]PsC microdomain acts as a “local store” for K+ to be returned to the ECS after neuronal excitation, thus preventing K+ undershoot . In particular, this could explain the slow decay rate of Na+ following a glutamate uptake through EAAT1/2. The formation of microdomains may have a pathological potential as alterations to the local intra- and extracellular homeostatic environment impairs neurotransmitters clearance from the synaptic cleft, therefore promoting network hyper-excitability.

Conference

Conference11th FENS (Federation of European Neuroscience Societies) Forum of Neuroscience
CountryGermany
CityBerlin
Period7/07/1811/07/18
Internet address

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Cations
Membranes
Carisoprodol
Neurotransmitter Agents
Glutamic Acid
Phospholipids
Ions
Lipids
Astrocytes

Cite this

Wade, J., Breslin, K., McDaid, LJ., Flanagan, B., Harkin, J., Wong-Lin, K., ... Van Zalinge, H. (Accepted/In press). Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle. Abstract from 11th FENS (Federation of European Neuroscience Societies) Forum of Neuroscience, Berlin, Germany.
Wade, John ; Breslin, Kevin ; McDaid, LJ ; Flanagan, Bronac ; Harkin, Jim ; Wong-Lin, KongFatt ; Verkhratsky, Alexei ; Hall, Steve ; Van Zalinge, Harm. / Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle. Abstract from 11th FENS (Federation of European Neuroscience Societies) Forum of Neuroscience, Berlin, Germany.
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title = "Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle",
abstract = "Recent studies have demonstrated that neuronal activity triggers transient increases in the cytosolic [Na+]PsC and [K+]PsC concentrations at the perisynaptic cradle (PsC). These microdomains strongly correlate with several crucial homeostatic pathways including K+ uptake by astrocytes and neuronal metabolic support. The aim of this poster is to present using mathematical modelling, a new hypothesis whereby microdomain formation is a direct result of fixed negatively charged ions associated with the dipole heads of membrane phospholipids. Specifically, we hypothesize that these negatively charged lipids result in deep potential wells near the dipole heads restricting the flow of cations in thin astrocyte processes to “hopping” between wells (well hopping) as they transverse the process. Results show that for very thin astrocyte processes, with a large surface to volume ratio, cation retention in wells dominates over conventional electrochemical diffusion (see Figure below). Essentially this low conductance pathway semi-isolates the PsC from the astrocytic soma allowing microdomains to form at the PsC. This has implications for K+ clearance as [K+]PsC microdomain acts as a “local store” for K+ to be returned to the ECS after neuronal excitation, thus preventing K+ undershoot . In particular, this could explain the slow decay rate of Na+ following a glutamate uptake through EAAT1/2. The formation of microdomains may have a pathological potential as alterations to the local intra- and extracellular homeostatic environment impairs neurotransmitters clearance from the synaptic cleft, therefore promoting network hyper-excitability.",
author = "John Wade and Kevin Breslin and LJ McDaid and Bronac Flanagan and Jim Harkin and KongFatt Wong-Lin and Alexei Verkhratsky and Steve Hall and {Van Zalinge}, Harm",
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Wade, J, Breslin, K, McDaid, LJ, Flanagan, B, Harkin, J, Wong-Lin, K, Verkhratsky, A, Hall, S & Van Zalinge, H 2018, 'Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle' 11th FENS (Federation of European Neuroscience Societies) Forum of Neuroscience, Berlin, Germany, 7/07/18 - 11/07/18, .

Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle. / Wade, John; Breslin, Kevin; McDaid, LJ; Flanagan, Bronac; Harkin, Jim; Wong-Lin, KongFatt; Verkhratsky, Alexei; Hall, Steve; Van Zalinge, Harm.

2018. Abstract from 11th FENS (Federation of European Neuroscience Societies) Forum of Neuroscience, Berlin, Germany.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle

AU - Wade, John

AU - Breslin, Kevin

AU - McDaid, LJ

AU - Flanagan, Bronac

AU - Harkin, Jim

AU - Wong-Lin, KongFatt

AU - Verkhratsky, Alexei

AU - Hall, Steve

AU - Van Zalinge, Harm

PY - 2018/4/9

Y1 - 2018/4/9

N2 - Recent studies have demonstrated that neuronal activity triggers transient increases in the cytosolic [Na+]PsC and [K+]PsC concentrations at the perisynaptic cradle (PsC). These microdomains strongly correlate with several crucial homeostatic pathways including K+ uptake by astrocytes and neuronal metabolic support. The aim of this poster is to present using mathematical modelling, a new hypothesis whereby microdomain formation is a direct result of fixed negatively charged ions associated with the dipole heads of membrane phospholipids. Specifically, we hypothesize that these negatively charged lipids result in deep potential wells near the dipole heads restricting the flow of cations in thin astrocyte processes to “hopping” between wells (well hopping) as they transverse the process. Results show that for very thin astrocyte processes, with a large surface to volume ratio, cation retention in wells dominates over conventional electrochemical diffusion (see Figure below). Essentially this low conductance pathway semi-isolates the PsC from the astrocytic soma allowing microdomains to form at the PsC. This has implications for K+ clearance as [K+]PsC microdomain acts as a “local store” for K+ to be returned to the ECS after neuronal excitation, thus preventing K+ undershoot . In particular, this could explain the slow decay rate of Na+ following a glutamate uptake through EAAT1/2. The formation of microdomains may have a pathological potential as alterations to the local intra- and extracellular homeostatic environment impairs neurotransmitters clearance from the synaptic cleft, therefore promoting network hyper-excitability.

AB - Recent studies have demonstrated that neuronal activity triggers transient increases in the cytosolic [Na+]PsC and [K+]PsC concentrations at the perisynaptic cradle (PsC). These microdomains strongly correlate with several crucial homeostatic pathways including K+ uptake by astrocytes and neuronal metabolic support. The aim of this poster is to present using mathematical modelling, a new hypothesis whereby microdomain formation is a direct result of fixed negatively charged ions associated with the dipole heads of membrane phospholipids. Specifically, we hypothesize that these negatively charged lipids result in deep potential wells near the dipole heads restricting the flow of cations in thin astrocyte processes to “hopping” between wells (well hopping) as they transverse the process. Results show that for very thin astrocyte processes, with a large surface to volume ratio, cation retention in wells dominates over conventional electrochemical diffusion (see Figure below). Essentially this low conductance pathway semi-isolates the PsC from the astrocytic soma allowing microdomains to form at the PsC. This has implications for K+ clearance as [K+]PsC microdomain acts as a “local store” for K+ to be returned to the ECS after neuronal excitation, thus preventing K+ undershoot . In particular, this could explain the slow decay rate of Na+ following a glutamate uptake through EAAT1/2. The formation of microdomains may have a pathological potential as alterations to the local intra- and extracellular homeostatic environment impairs neurotransmitters clearance from the synaptic cleft, therefore promoting network hyper-excitability.

M3 - Abstract

ER -

Wade J, Breslin K, McDaid LJ, Flanagan B, Harkin J, Wong-Lin K et al. Cation Retention in Membrane Potential Wells: Ionic Microdomain Formation at the Perisynaptic Cradle. 2018. Abstract from 11th FENS (Federation of European Neuroscience Societies) Forum of Neuroscience, Berlin, Germany.