Cell swelling activates a large Cl− current. A representative whole-cell recording of currents in an MLS-9 cell in response to voltage ramps from −100 to +80 mV, from a holding potential of −10 mV. (A) The first five sweeps show a very small current in iso-osmotic NMDG+ bath solution (Solution 4; 177 mOsm/kgH2O; see Methods). When the bath was perfused with the hypo-osmotic Solution 5, the cell swelled (inset) and an outward-rectifying current activated, increased with time (vertical arrow) and reached a quasi-stationary plateau. (B) When re-exposed to iso-osmotic bath (Solution 4), the cell shrank (inset) and the current declined to its pre-swelling level. (C) The instantaneous slope conductance was calculated at the experimentally measured reversal potential (Erev) by fitting each current trace with a mono-exponential function and taking the derivative at Erev. The instantaneous slope conductance was then normalized to the cell size (capacitance in pF), and plotted as a function of time after establishing the whole-cell recording. Current activation and deactivation are shown during two cycles of swelling and shrinking (same cell as in A and B).