Research

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

Petra Ehling^1* , Stefan Bittner^2* , Nicole Bobak³ , Tobias Schwarz² , Heinz Wiendl³ , Thomas Budde¹ , Christoph Kleinschnitz^2* and Sven G Meuth^2,3*

¹  Westfaelische Wilhelms-University Muenster, Institute of Physiology I, Robert-Koch Str. 27a, 48149 Muenster, Germany

²  University of Wuerzburg, Department of Neurology, Josef-Schneider Str. 11, 97080 Wuerzburg, Germany

³  University of Muenster, Neurological Clinic - Inflammatory Disorders of the Central Nerveous System and Neurooncology, Mendelstr. 7, 48149 Muenster, Germany

author email corresponding author email* Contributed equally

Experimental & Translational Stroke Medicine 2010, 2:14doi:10.1186/2040-7378-2-14

Published:	20 July 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.