BK Channels Mediate Pathway-Specific Modulation of Visual Signals in theIn VivoMouse Retina

The modulatory role of large-conductance Ca2+-activated K+(BK) channels in the nervous system has been extensively studied. In the retina, it has been shown that BK channels play a pivotal role in modulating feedback from A17 amacrine cells to rod bipolar cells (RBCs). Here, we used electroretinography to examine the functional role of BK channels for rod and cone vision in the retinain vivousing a genetically engineered mouse lacking functional BK channels (Bk−/−). Under dark-adapted and light-adapted conditions, the lack of BK channels had no effect on photoreceptor activity, suggesting that these ion channels do not modulate photoreceptor responses. At the bipolar cell level, the ERG signals attributed to RBCs inBk−/−mice were not different from those in wild-type mice at low scotopic stimulus intensities. However, at high scotopic and low mesopic stimulus intensities, close to RBC saturation, a significant reduction of ERG signals reflecting RBC activity was present in theBk−/−retina. At higher mesopic stimulus intensities activating both RBCs and cone bipolar cells (CBCs), no difference in ERG signals betweenBk−/−and wild-type mice was found. In photopic stimulus paradigms, activity of ON- and OFF-CBCs inBk−/−and wild-type retinae was indistinguishable. These findings demonstrate that BK channels modulate visual responsesin vivoat the bipolar cell level at intermediate stimulus conditions.