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. 2008 Nov 5;28(45):11488–11499. doi: 10.1523/JNEUROSCI.2431-08.2008

Figure 1.

Figure 1.

Aβ peptide increases CLIC1-mediated membrane chloride current in microglial cells. a, Perforated-patch current recordings from BV2 cells during 20 mV voltage steps from −60 to +80 mV from a holding potential of −50 mV. Traces show (from top to bottom) the following: membrane current in control conditions, perfused with 50 μm IAA94 and 200 μm DIDS then washed, during exposure to 50 μm Aβ25–35; after the current increase reached a plateau and in the constant presence of Aβ25–35, 50 μm IAA94 was added to the solution, followed by 200 μm DIDS, followed by washout of the current blockers. b, Subtracted currents, showing the components sensitive to IAA94 (411.3 ± 11.6 pA) and DIDS (109.8 ± 8.5 pA), respectively (inset), and the current–voltage relationships of the IAA94- (squares) and DIDS- (circles) sensitive currents. Both currents show reversal potentials close to the Cl− equilibrium potential given our experimental conditions (−45.4 ± 2.7 mV and −42.7 ± 2.2 mV, respectively; n = 9). c, Time course of the BV2 microglial cell membrane current amplitude measured at 700 ms of an 800 ms voltage step from −50/+50 mV, delivered every 10 s. Starting from a steady value, the cell was perfused with Aβ25–35. After 5–15 min, the current increased, reaching a plateau over 10–20 min (n = 21). Application of IAA94 reduced the current amplitude from 339.5 ± 21.6 pA to 118.3 ± 12.1 pA (n = 21; p < 0.001, independent samples t test) which was further reduced by 200 μm DIDS. The opposite sequence of chloride channel blockers was then followed, showing that IAA94 and DIDS act on different targets. d, Membrane potential measurements during Aβ exposure. Shown is an example in which a microglial cell depolarized from −75 mV to −43 mV after perfusion with Aβ25–35 (50 μm); after reaching a plateau, addition of 50 μm IAA94 prompted a further 25 mV depolarization. The effect of the chloride channel blocker was completely reversible. e, In a similar experiment from another cell, 3 mm zinc had no effect on the membrane depolarization caused by Aβ. The effect of IAA94 was still evident.