Downregulation of potassium chloride cotransporter KCC2 after transient focal cerebral ischemia.
OBJECTIVE
The potassium chloride cotransporter 2 (KCC2) is the main neuronal chloride extruder in the adult nervous system. Therefore, KCC2 is responsible for an inwardly directed electrochemical gradient of chloride that leads to hyperpolarizing GABA-mediated responses. Under some pathophysiological conditions, GABA has been reported to be depolarizing because of a downregulation of KCC2. This is the first study to our knowledge analyzing the expression of KCC2 after a focal cerebral ischemia.


METHODS
Mild and severe ischemia were induced in rats by a transient occlusion of the middle cerebral artery for 30 and 120 minutes, respectively. KCC2 mRNA and protein expression were studied in the ischemic hemisphere after different reperfusion times (2 hour, 1 day, 7 days, 30 days, 168 days) by using quantitative polymerase chain reaction, Western blotting, and immunohistological staining.


RESULTS
We found a substantial decrease of KCC2 mRNA and protein levels in the ischemic hemisphere, with a stronger downregulation of KCC2 after severe vs mild ischemia. Long-term surviving cells expressing KCC2 could be detected in the infarct core. These cells were identified as GABAergic interneurons mainly expressing parvalbumin.


CONCLUSIONS
Our study revealed a substantial neuron-specific downregulation of KCC2 after focal cerebral ischemia.
Jaenisch
Nadine
N
Hans-Berger Clinic for Neurology, Friedrich-Schiller University, Erlanger Allee 101, 07747 Jena, Germany. christiane.frahm@med.uni-jena.de
Witte
Otto W
OW
Frahm
Christiane
C
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011188:Potassium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D000096922:K Cl- Cotransporters
D002712:Chlorides; D011188:Potassium; D012333:RNA, Messenger; D027981:Symporters; D000096922:K Cl- Cotransporters