The Role of the Ca²⁺-activated Cl^- Conductance in the Membrane Potential and Light Response of Mouse Rods

To characterize the function of the Ca²⁺-activated Cl^- current I _Cl(Ca) in mammalian rod photoreceptors, we made patch-clamp recordings from retinal slices of mice (Mus musculus) of both sexes that lack Ano2 (TMEM16B). Depolarizing voltage ramps in solutions blocking K⁺ currents elicited a large outward current inhibited by the Cl^- channel blocker niflumic acid; this current was absent in Ano2^-/- rods. The membrane potential of Ano2^-/- rods was 10-15 mV more depolarized in darkness than WT or Cx36^-/- rods, indicating a substantial resting Cl^- permeability. Rod outer-segment photocurrents were similar in waveform and amplitude in Ano2^-/- and Cx36^-/- rods, but photovoltages in Ano2^-/- rods were nearly doubled. Measurements of light-response reversal potentials in rods with and without Ano2 suggest that the outer-segment conductance is nearly linear with a reversal potential of -9 mV and that [Formula: see text] increases during the light response. Using these results, we estimated E _Cl from permeabilized patch recordings of reversal potentials of Cx36^-/- rods to have a mean value of -35 mV near the rod resting potential, but other evidence suggests that E _Cl may be more positive by as much as 10-15 mV. Thus activation of I _Cl(Ca) during the light response would be depolarizing. At dim intensities, the photocurrents of downstream rod bipolar cells were larger and about twice as sensitive in Ano2^-/- retinas with reduced nonlinearity. These experiments show that Ca²⁺-activated Cl^- currents in mammalian rods have more important roles in photoreceptor physiology than previously appreciated.