Fig. 8
From: Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels
CLC-3 activation regulates GABA excitation in the developing neurons. a Epileptiform burst activity induced by 0 Mg2+ aCSF in neonatal CA3 neurons showed long-lasting membrane depolarization. b A long-lasting membrane depolarization pulse (40 mV, 10 s), mimicking the epileptiform burst activity, which significantly enhanced the inward GABAA-R current (actually Cl− efflux trough the GABAA-R) induced by GABAA-R agonist isoguvacine (100 μM) under gramicidin-perforated whole-cell recording. Such depolarization-induced enhancement was absent in CLC-3 KO mice and strongly inhibited by CLC-3 channel blocker NaGluc (20 mM). c Summarized data of the long-lasting membrane depolarization effect on the inward GABAA-R current in WT, CLC-3 KO, and WT + NaGluc groups. ** P < 0.01. d Typical traces of cell-attached recording showing the spike activity induced by isoguvacine (10 μM, 30 s) under different conditions in neonatal animals (P8–9). e Summarized data showing the percentage of neurons excited by isoguvacine. Note that CLC-3 KO and NaGluc significantly inhibited the GABA excitatory activity induced by 0 Mg2+ aCSF. f Comparison between the effects of bumetanide and NaGluc on epileptiform activity induced by 0 Mg2+ in neonatal brain slices. g, h Power analysis illustrated a significant reduction of power after NaGluc application (68.9% reduction in presence of NaGluc, P < 0.001, paired Student’s t-test) but not bumetanide application (P > 0.7, paired Student’s t-test). Data are shown as mean ± s.e.m