Large-conductance Ca2+-activated potassium channels are potently involved in the inverse neurovascular response to spreading depolarization

Ákos Menyhárt, Attila E. Farkas, Dániel P. Varga, Rita Frank, Réka Tóth, Armand R. Bálint, Péter Makra, Jens P. Dreier, F. Bari, I. Krizbai, E. Farkas

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recurrent spreading depolarizations occur in the cerebral cortex from minutes up to weeks following acute brain injury. Clinical evidence suggests that the immediate reduction of cerebral blood flow in response to spreading depolarization importantly contributes to lesion progression as the wave propagates over vulnerable tissue zones, characterized by potassium concentration already elevated prior to the passage of spreading depolarization. Here we demonstrate with two-photon microscopy in anesthetized mice that initial vasoconstriction in response to SD triggered experimentally with 1 M KCl is coincident in space and time with the large extracellular accumulation of potassium, as shown with a potassium indicator fluorescent dye. Moreover, pharmacological manipulations in combination with the use of potassium-sensitive microelectrodes suggest that large-conductance Ca2+-activated potassium (BK) channels and L-type voltage-gated calcium channels play significant roles in the marked initial vasoconstriction under elevated baseline potassium. We propose that potassium efflux through BK channels is a central component in the devastating neurovascular effects of spreading depolarizations in tissue at risk.

Original languageEnglish
Pages (from-to)41-52
Number of pages12
JournalNeurobiology of Disease
Volume119
DOIs
Publication statusPublished - Nov 1 2018

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Potassium Channels
Potassium
Large-Conductance Calcium-Activated Potassium Channels
Vasoconstriction
Cerebrovascular Circulation
Microelectrodes
Calcium Channels
Fluorescent Dyes
Photons
Cerebral Cortex
Brain Injuries
Microscopy
Pharmacology

Keywords

  • Calcium channels
  • Cerebral arteriole
  • Cerebral blood flow
  • Neurovascular coupling
  • Paxilline
  • Potassium
  • Potassium channels
  • Spreading depression
  • Spreading ischemia
  • Vasoconstriction

ASJC Scopus subject areas

  • Neurology

Cite this

Large-conductance Ca2+-activated potassium channels are potently involved in the inverse neurovascular response to spreading depolarization. / Menyhárt, Ákos; Farkas, Attila E.; Varga, Dániel P.; Frank, Rita; Tóth, Réka; Bálint, Armand R.; Makra, Péter; Dreier, Jens P.; Bari, F.; Krizbai, I.; Farkas, E.

In: Neurobiology of Disease, Vol. 119, 01.11.2018, p. 41-52.

Research output: Contribution to journalArticle

Menyhárt, Ákos ; Farkas, Attila E. ; Varga, Dániel P. ; Frank, Rita ; Tóth, Réka ; Bálint, Armand R. ; Makra, Péter ; Dreier, Jens P. ; Bari, F. ; Krizbai, I. ; Farkas, E. / Large-conductance Ca2+-activated potassium channels are potently involved in the inverse neurovascular response to spreading depolarization. In: Neurobiology of Disease. 2018 ; Vol. 119. pp. 41-52.
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