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 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.