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Epilepsy

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開催日
2010年09月04日(土)
時 間
13:00 - 14:00
会 場
Poster Room 2

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Cation-chloride co-transportors are involved in cyclothiazide induced depolarizing shift of EGABA in CA1 pyramid neurons

演題番号 : P3-n28

Zheng Wu:1 

1:Institutes of Brain Science and State Key Laboratory for Medical Neurobiology 

 

Imbalance between inhibitory and excitatory in the brain is one of the basic mechanisms for epileptogenesis. Previous study from our lab has shown that cyclothiazide (CTZ) is a potent convulsant in inducing epilepsy both in vitro and in vivo by activating glutamatergic and suppressing GABAergic transmission. Activation of iGABA-receptors induced fast response depends on the concentration gradient of intracellular and extracellular chloridion, which is regulated partly by cation-chloride co-transportors (CCCs). The aim of current study is to investigate the functional role of CCCs in CTZ induced epileptogenesis. Rat (P21-P30) hippocampal slices were incubated with 50 μM CTZ for 2 hours before evoked field potential responses were recorded from CA1 pyramidal layer. CTZ induced evoked population spikes and a significant depolarizing shift in EGABA (Control = -71.48 ± 1.44 mV, n = 9 vs CTZ = -58.14 ± 1.62 mV, n = 8, p<0.01, using gramicidin perforated whole cell techniques; control = -62.56 ± 1.06 mV, n = 14 vs CTZ = -56.15 ± 0.93 mV, n=11, p<0.01, using whole cell recording ) in CA1 pyramid neurons . To determine the contributions of CCCs in setting EGABA under these conditions, furosemide and bumetanide, two CCCs inhibitors, were tested on their effect on EGABA. Consistent with previous reports, furosemide alone also caused a positive shift of EGABA (100 μM, -57.58 ± 1.51 mV, n = 9; p<0.01 ) but not the bumetanide (10 μM, -63.58 ± 1.80 mV, n = 10 ). Our present results demonstrate that down-regulation of KCC2 activity may contribute to the CTZ-induced high neuron activity in hippocampal CA1 pyramidal layer

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