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Experimental & Translational Stroke Medicine

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Open Access 01-12-2010 | Research

Two pore domain potassium channels in cerebral ischemia: a focus on K_2P9.1 (TASK3, KCNK9)

Authors: Petra Ehling, Stefan Bittner, Nicole Bobak, Tobias Schwarz, Heinz Wiendl, Thomas Budde, Christoph Kleinschnitz, Sven G Meuth

Published in: Experimental & Translational Stroke Medicine | Issue 1/2010

Abstract

Background

Recently, members of the two-pore domain potassium channel family (K_2P channels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K_2P3.1^-/- animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K_2P channel K_2P9.1.

Methods

We combine electrophysiological recordings in brain-slice preparations of wildtype and K_2P9.1^-/- mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K_2P9.1 in stroke formation.

Results

Patch-clamp recordings reveal that currents mediated through K_2P9.1 can be obtained in slice preparations of the dorsal lateral geniculate nucleus (dLGN) as a model of central nervous relay neurons. Current characteristics are indicative of K_2P9.1 as they display an increase upon removal of extracellular divalent cations, an outward rectification and a reversal potential close to the potassium equilibrium potential. Lowering extracellular pH values from 7.35 to 6.0 showed comparable current reductions in neurons from wildtype and K_2P9.1^-/- mice (68.31 ± 9.80% and 69.92 ± 11.65%, respectively). These results could be translated in an in vivo model of cerebral ischemia where infarct volumes and functional outcomes showed a none significant tendency towards smaller infarct volumes in K_2P9.1^-/- animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 ± 17.31 mm³ and 47.10 ± 19.26 mm³, respectively).

Conclusions

Together with findings from earlier studies on K_2P2.1^-/- and K_2P3.1^-/- mice, the results of the present study on K_2P9.1^-/- mice indicate a differential contribution of K_2P channel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia.

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Title: Two pore domain potassium channels in cerebral ischemia: a focus on K2P9.1 (TASK3, KCNK9)
Authors: Petra Ehling
Stefan Bittner
Nicole Bobak
Tobias Schwarz
Heinz Wiendl
Thomas Budde
Christoph Kleinschnitz
Sven G Meuth
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Experimental & Translational Stroke Medicine / Issue 1/2010
Electronic ISSN: 2040-7378
DOI: https://doi.org/10.1186/2040-7378-2-14

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Two pore domain potassium channels in cerebral ischemia: a focus on K_2P9.1 (TASK3, KCNK9)

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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