Unknown

Dataset Information

0

The neuroprotective impact of the leak potassium channel TASK1 on stroke development in mice.


ABSTRACT: Oxygen depletion (O(2)) and a decrease in pH are initial pathophysiological events in stroke development, but secondary mechanisms of ischemic cell death are incompletely understood. By patch-clamp recordings of brain slice preparations we show that TASK1 and TASK3 channels are inhibited by pH-reduction (42+/-2%) and O(2) deprivation (36+/-5%) leading to membrane depolarization, increased input resistance and a switch in action potential generation under ischemic conditions. In vivo TASK blockade by anandamide significantly increased infarct volumes at 24 h in mice undergoing 30 min of transient middle cerebral artery occlusion (tMCAO). Moreover, blockade of TASK channels accelerated stroke development. Supporting these findings TASK1(-/-) mice developed significantly larger infarct volumes after tMCAO accompanied by worse outcome in functional neurological tests compared to wild type mice. In conclusion, our data provide evidence for an important role of functional TASK channels in limiting tissue damage during cerebral ischemia.

SUBMITTER: Meuth SG 

PROVIDER: S-EPMC3714864 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

The neuroprotective impact of the leak potassium channel TASK1 on stroke development in mice.

Meuth Sven G SG   Kleinschnitz Christoph C   Broicher Tilman T   Austinat Madeleine M   Braeuninger Stefan S   Bittner Stefan S   Fischer Stephan S   Bayliss Douglas A DA   Budde Thomas T   Stoll Guido G   Wiendl Heinz H  

Neurobiology of disease 20080930 1


Oxygen depletion (O(2)) and a decrease in pH are initial pathophysiological events in stroke development, but secondary mechanisms of ischemic cell death are incompletely understood. By patch-clamp recordings of brain slice preparations we show that TASK1 and TASK3 channels are inhibited by pH-reduction (42+/-2%) and O(2) deprivation (36+/-5%) leading to membrane depolarization, increased input resistance and a switch in action potential generation under ischemic conditions. In vivo TASK blockad  ...[more]

Similar Datasets

| S-EPMC3130955 | biostudies-literature
| S-EPMC4161023 | biostudies-literature
| S-EPMC6176580 | biostudies-literature
| S-EPMC2206116 | biostudies-literature
| S-EPMC2410027 | biostudies-literature
| S-EPMC2716456 | biostudies-literature
| S-EPMC6632358 | biostudies-literature
| S-EPMC7515701 | biostudies-literature
| S-EPMC24080 | biostudies-literature
| S-EPMC5469303 | biostudies-literature