Calcium sensitive non-selective cation current promotes seizure-like discharges and spreading depression in a model neuron |
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Authors: | G G Somjen H Kager W J Wadman |
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Institution: | (1) Department of Cell Biology, Duke University Medical Center, Box 3011, Durham, NC 27710, USA;(2) SILS-Center for NeuroScience, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands |
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Abstract: | As described by others, an extracellular calcium-sensitive non-selective cation channel (Ca2+]o-sensitive NSCC) of central neurons opens when extracellular calcium level decreases. An other non-selective current is activated
by rising intracellular calcium (Ca2+]
i
). The Ca2+]o-sensitive NSCC is not dependent on voltage and while it is permeable by monovalent cations, it is blocked by divalent cations.
We tested the hypothesis that activation of this channel can promote seizures and spreading depression (SD). We used a computer
model of a neuron surrounded by interstitial space and enveloped in a glia-endothelial “buffer” system. Na+, K+, Ca2+ and Cl− concentrations, ion fluxes and osmotically driven volume changes were computed. Conventional ion channels and the NSCC were
incorporated in the neuron membrane. Activation of NSCC conductance caused the appearance of paroxysmal afterdischarges (ADs)
at parameter settings that did not produce AD in the absence of NSCC. The duration of the AD depended on the amplitude of
the NSCC. Similarly, NSCC also enabled the generation of SD. We conclude that NSCC can contribute to the generation of epileptiform
events and to spreading depression. |
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Keywords: | Calcium depletion Calcium dependent current Non-specific cation current Epilepsy Seizure mechanisms Spreading depression |
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