Structure of a volume-regulated chloride channel: the view from above shows the selectivity filter. (Image: Raimund Dutzler, UZH).
Human cells are enclosed by membranes and are in osmotic equilibrium with their environment. If the concentration of solute molecules (osmolarity) in the fluid surrounding the cells decreases, cells start to swell; in extreme cases, this can result in the cells bursting. To avoid this, cells activate volume-regulated chloride channels (VRACs) of the LRRC8 protein family. If the cell volume increases as a result of inflowing water, these cellular valves open to allow the negatively charged chloride ions and uncharged osmolytes to flow out, returning the cell to its original state. Structure of a volume-regulated anion channel. Although discovered only five years ago, important properties of these cellular valves have already been described. For example, it is known that, besides their role in volume regulation, VRACs play an important role for the uptake of drugs used in cancer therapy and that they are responsible for the uncontrolled release of neurotransmitters after a stroke.
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