The two-pore domain potassium channel KCNK5 deteriorates outcome in ischemic neurodegeneration.

The two-pore domain potassium channel KCNK5 deteriorates outcome in ischemic neurodegeneration. Pflugers Arch. 2014 Oct 15; Authors: Göb E, Bittner S, Bobak N, Kraft P, Göbel K, Langhauser F, Homola GA, Brede M, Budde T, Meuth SG, Kleinschnitz C Abstract Potassium channels can fulfill both beneficial and detrimental roles in neuronal damage during ischemic stroke. Earlier studies have characterized a neuroprotective role of the two-pore domain potassium channels KCNK2 (TREK1) and KCNK3 (TASK1). Protective neuronal hyperpolarization and prevention of intracellular Ca(2+) overload and glutamate excitotoxicity were suggested to be the underlying mechanisms. We here identify an unexpected role for the related KCNK5 channel in a mouse model of transient middle cerebral artery occlusion (tMCAO). KCNK5 is strongly upregulated on neurons upon cerebral ischemia, where it is most likely involved in the induction of neuronal apoptosis. Hypoxic conditions elevated neuronal expression levels of KCNK5 in acute brain slices and primary isolated neuronal cell cultures. In agreement, KCNK5 knockout mice had significantly reduced infarct volumes and improved neurologic function 24 h after 60 min of tMCAO and this protective effect was preserved at later stages of infarct development. KCNK5 deficiency resulted in a significantly reduced number of apoptotic neurons, a downregulation of pro-apoptotic and upregulation of anti-apoptotic factors. Result...
Source: Pflugers Archiv : European Journal of Physiology - Category: Physiology Authors: Tags: Pflugers Arch Source Type: research