Two pore domain potassium channels in cerebral ischemia: a focus on K2P9.1 (TASK3, KCNK9).
Recently, members of the two-pore domain potassium channel family (K2P channels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K2P3.1-/- animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K2P channel K2P9.1.



We combine electrophysiological recordings in brain-slice preparations of wildtype and K2P9.1-/- mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K2P9.1 in stroke formation.



Patch-clamp recordings reveal that currents mediated through K2P9.1 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 K2P9.1 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 K2P9.1-/- 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 K2P9.1-/- 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).



Together with findings from earlier studies on K2P2.1-/- and K2P3.1-/- mice, the results of the present study on K2P9.1-/- mice indicate a differential contribution of K2P channel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia.
Ehling
Petra
P
Westfaelische Wilhelms-University Muenster, Institute of Physiology I, Robert-Koch Str. 27a, 48149 Muenster, Germany.
Bittner
Stefan
S
University of Wuerzburg, Department of Neurology, Josef-Schneider Str. 11, 97080 Wuerzburg, Germany.
Bobak
Nicole
N
University of Muenster, Neurological Clinic - Inflammatory Disorders of the Central Nerveous System and Neurooncology, Mendelstr. 7, 48149 Muenster, Germany.
Schwarz
Tobias
T
University of Wuerzburg, Department of Neurology, Josef-Schneider Str. 11, 97080 Wuerzburg, Germany.
Wiendl
Heinz
H
University of Muenster, Neurological Clinic - Inflammatory Disorders of the Central Nerveous System and Neurooncology, Mendelstr. 7, 48149 Muenster, Germany.
Budde
Thomas
T
Westfaelische Wilhelms-University Muenster, Institute of Physiology I, Robert-Koch Str. 27a, 48149 Muenster, Germany.
Kleinschnitz
Christoph
C
University of Wuerzburg, Department of Neurology, Josef-Schneider Str. 11, 97080 Wuerzburg, Germany.
Meuth
Sven G
SG
University of Wuerzburg, Department of Neurology, Josef-Schneider Str. 11, 97080 Wuerzburg, Germany.|University of Muenster, Neurological Clinic - Inflammatory Disorders of the Central Nerveous System and Neurooncology, Mendelstr. 7, 48149 Muenster, Germany.