Fig. 8.

Model of presynaptic silencing in neuromast organs. Left-side, Model 1: low [K⁺]_in is causative for Ca_V1.3 channel (red) activation. In active cells, (1) similar to glia, supporting cells may use Kir4.1 channels (green) to take up [K⁺]_ex, gap junctions (Cx, blue) to spatially buffer K⁺ among syncytia of supporting cells, and a K⁺-Cl⁻ cotransporter such as KCC3 (yellow) to clear K⁺ from supporting cells. This results in (2) lower [K⁺]_in in active cells. Cells with lower [K⁺]_in may be at sufficiently depolarized resting membrane potentials where (3) mechanosensation and depolarization (∆V) is able to (4) activate Ca_V1.3 channels. In this model, despite K⁺ buffering by supporting cells, not all hair cells are able to be maintained with [K⁺]_in levels low enough to facilitate presynaptic function. Blocking gap junctions elevates hair-cell [K⁺]_in and presynaptic function is lost in all cells. After laser damage (green lightning bolt), a signaling cascade could lower [K⁺]_in levels in silent cells, and raise resting membrane potentials into a range suitable for Ca_V1.3 channel activation. Right-side, Model 2: low [K⁺]_in is a consequence of presynaptic activity. This schematic demonstrates that (1) mechanosensation and depolarization (∆V), lead to (2) Ca_V1.3 channel activation in active cells. Presynaptic activity results in (3) lower [K⁺]_in. In this model, Ca_V1.3 channels may be inactive due to a lack of biochemical modification, such as phosphorylation (P), as shown in this example. Alternatively, Ca_V1.3 channels could also be rendered inactive due to a missing interaction partner or improper assembly at the plasma membrane (these examples not shown). In this example, after laser damage (green lightning bolt), a signaling cascade could promote phosphorylation and lead to Ca_V1.3 channel activation