Fig. 2. Channels and transporters involved in cell volume regulation in keratinocytes (modified from [18]). Hypotonic stress leads to cell swelling by an influx of water, which is then counteracted by regulatory volume decrease (RVD) (left). In keratinocytes, RVD is mediated by release of K⁺, Cl^- and organic osmolytes through volume-regulated anion channels (VRACs) such as LRRC8, two-pore-domain K⁺ channels (K2P) and Ca²⁺-activated K⁺ or Cl^- channels (e.g. SK4 and BK). The efflux of osmolytes during RVD is supported by an influx of Ca²⁺ e.g. via TRPV4. Release of these osmolytes from the cytoplasm into the extracellular space alters the osmotic gradient and is therefore accompanied by water efflux. On the other hand, hypertonic stress leads to cell shrinkage due to water loss, which is counteracted by regulatory volume increase (RVI) (right). In keratinocytes, organic osmolyte transporters (like TAUT and BGT-1) can counteract this water movement by mediating the uptake of organic osmolytes. Additionally, activation of Na⁺/H⁺ exchanger 1 (NHE1) was described in keratinocytes and can mediate influx of Na⁺. This increase in intracellular osmolyte concentrations mediates an influx of water, which restores the initial cell volume.