Two pore domain potassium channels in cerebral ischemia: a focus on $ K_{2P} $9.1 (TASK3, KCNK9)

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_{2P} $3.$ 1^{-/-} $ animals showed larger infarct volumes and a worse functional outcome followi...
Ausführliche Beschreibung

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_{2P} $3.$ 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_{2P} $9.1. Methods We combine electrophysiological recordings in brain-slice preparations of wildtype and $ K_{2P} $9.$ 1^{-/-} $ mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of $ K_{2P} $9.1 in stroke formation. Results Patch-clamp recordings reveal that currents mediated through $ K_{2P} $9.1 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_{2P} $9.1 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_{2P} $9.$ 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_{2P} $9.$ 1^{-/-} $ animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 ± 17.31 $ mm^{3} $ and 47.10 ± 19.26 $ mm^{3} $, respectively). Conclusions Together with findings from earlier studies on $ K_{2P} $2.$ 1^{-/-} $ and $ K_{2P} $3.$ 1^{-/-} $ mice, the results of the present study on $ K_{2P} $9.$ 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. Ausführliche Beschreibung