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Astrocytic gap junction blockade markedly increases extracellular potassium without causing seizures in the mouse neocortex.
Bazzigaluppi, Paolo; Weisspapir, Iliya; Stefanovic, Bojana; Leybaert, Luc; Carlen, Peter L.
Afiliação
  • Bazzigaluppi P; Fundamental Neurobiology, Krembil Research Institute, University Health Network, M5T 2S8 Toronto, Ontario, Canada; Physical Sciences, Sunnybrook Research Institute, M4N 3M5 Toronto, Ontario, Canada. Electronic address: paolo.bazzigaluppi@gmail.com.
  • Weisspapir I; Fundamental Neurobiology, Krembil Research Institute, University Health Network, M5T 2S8 Toronto, Ontario, Canada.
  • Stefanovic B; Physical Sciences, Sunnybrook Research Institute, M4N 3M5 Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Ontario, Canada.
  • Leybaert L; Department of Basic Medical Sciences, University of Ghent, 9000 Ghent, Belgium.
  • Carlen PL; Fundamental Neurobiology, Krembil Research Institute, University Health Network, M5T 2S8 Toronto, Ontario, Canada.
Neurobiol Dis ; 101: 1-7, 2017 May.
Article em En | MEDLINE | ID: mdl-28007587
ABSTRACT
Extracellular potassium concentration, [K+]o, is a major determinant of neuronal excitability. In the healthy brain, [K+]o levels are tightly controlled. During seizures, [K+]o increases up to 15mM and is thought to cause seizures due to its depolarizing effect. Although astrocytes have been suggested to play a key role in the redistribution (or spatial buffering) of excess K+ through Connexin-43 (Cx43)-based Gap Junctions (GJs), the relation between this dynamic regulatory process and seizure generation remains unknown. Here we contrasted the role of astrocytic GJs and hemichannels by studying the effect of GJ and hemichannel blockers on [K+]o regulation in vivo. [K+]o was measured by K+-sensitive microelectrodes. Neuronal excitability was estimated by local field potential (LFP) responses to forepaw stimulation and changes in the power of resting state activity. Starting at the baseline [K+]o level of 1.61±0.3mM, cortical microinjection of CBX, a broad spectrum connexin channel blocker, increased [K+]o to 11±3mM, Cx43 GJ/hemichannel blocker Gap27 increased it from 1.9±0.7 to 9±1mM. At these [K+]o levels, no seizures were observed. Cx43 hemichannel blockade with TAT-Gap19 increased [K+]o by only ~1mM. Microinjection of 4-aminopyridine, a known convulsant, increased [K+]o to ~10mM and induced spontaneously recurring seizures, whereas direct application of K+ did not trigger seizure activity. These findings are the first in vivo demonstration that astrocytic GJs are major determinants for the spatial buffering of [K+]o and that an increase in [K+]o alone does not trigger seizures in the neocortex.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Potássio / Astrócitos / Junções Comunicantes / Neocórtex Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Potássio / Astrócitos / Junções Comunicantes / Neocórtex Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article