Enhanced expressions of arachidonic acid-sensitive tandem-pore domain potassium channels in rat experimental acute cerebral ischemia

doi:10.1016/j.bbrc.2004.12.124

Biochemical and Biophysical Research Communications

Volume 327, Issue 4, 25 February 2005, Pages 1163-1169

https://doi.org/10.1016/j.bbrc.2004.12.124 Get rights and content

Abstract

To further explore the pathophysiological significance of arachidonic acid-sensitive potassium channels, RT-PCR and Western blot analysis were used to investigate the expression changes of TREK channels in cortex and hippocampus in rat experimental acute cerebral ischemia in this study. Results showed that TREK-1 and TRAAK mRNA in cortex, TREK-1 and TREK-2 mRNA in hippocampus showed significant increases 2 h after middle cerebral artery occlusion (MCAO). While the mRNA expression levels of the all three channel subtypes increased significantly 24 h after MCAO in cortex and hippocampus. At the same time, the protein expressions of all the three channel proteins showed significant increase 24 h after MCAO in cortex and hippocampus, but only TREK-1 showed increased expression 2 h after MCAO in cortex and hippocampus. Immunohistochemical experiments verified that all the three channel proteins had higher expression levels in cortical and hippocampal neurons 24 h after MCAO. These results suggested a strong correlation between TREK channels and acute cerebral ischemia. TREK channels might provide a neuroprotective mechanism in the pathological process.

Section snippets

Materials and methods

Experimental acute cerebral ischemia. Adult male Wistar rats weighing 260–300 g were used and were provided by the Animal Center of Chinese Academy of Medical Sciences, Beijing, China. MCAO model was used to produce rat acute cerebral ischemia [10]. Rats were divided into sham, ischemia for 2 h and ischemia for 24 h groups (n = 5). Briefly, rats were anesthetized and placed in a supine position. The common carotid (CCA), external carotid (ECA), internal carotid (ICA), and pterygopalatine (PPA)

mRNA expression changes of TREK-1, TREK-2, and TRAAK in cortex and hippocampus after MCAO

mRNA expression changes of TREK-1, TREK-2, and TRAAK were detected in both cortex and hippocampus 2 and 24 h after MCAO. The specificity of RT-PCR products was confirmed by the results of agarose gel electrophoresis that yielded single product bands of the expected sizes in all cases. Fig. 1 shows that in cortex, 2 h after MCAO, TREK-1 and TRAAK mRNA expressions increased significantly, while all the three channel mRNA showed significantly enhanced expressions 24 h after MCAO compared with the

Discussion

Stroke, including occlusive stroke, is one of the leading causes of death and dependence in activities of daily living in the world. It can result in severe neuronal degeneration and consequent loss of brain functions. Recent developments have further advanced our knowledge of the cellular and molecular mechanisms, and have confirmed that cerebral ischemia gives rise to widespread alteration of gene expressions and regulations. However, the pathophysiological process and the protective

Acknowledgments

This study was supported by National 863 Foundation Project of China, No. 2004AA2Z3815. We thank Prof. Lin Li for her help in the immunohistochemical experiments. We are also grateful to Dr. Gareth Davey for his help in this research.

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Enhanced expressions of arachidonic acid-sensitive tandem-pore domain potassium channels in rat experimental acute cerebral ischemia

Abstract

Section snippets

Materials and methods

mRNA expression changes of TREK-1, TREK-2, and TRAAK in cortex and hippocampus after MCAO

Discussion

Acknowledgments

Trends Neurosci.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Trends Pharmacol. Sci.

J. Biol. Chem.

Brain Res. Mol. Brain Res.

J. Biol. Chem.

J. Biol. Chem.

Brain Res.

TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure

EMBO J.

TWIK-1, a ubiquitous human weakly inward rectifying K⁺ channel with a novel structure