Volume-sensitive transport systems and volume homeostasis in vertebrate red blood cells

Animal cells regulate their volume in the short term by controlling solute movements into and out of the cell. A quite of dissipative transport systems are involved which allow either regulatory volume increase (RVI) or decrease (RVD) responses depending upon the direction of the electrochemical gradients of the solutes. Many of these transporters have been identified at the molecular level and structure-function studies have identified transmembrane transport domains and cytoplasmic regulatory domains. In vertebrate red blood cells, protein phosphorylation appears to be central to the coordinated regulation of transporter activity. Inhibitors of protein phosphatases (PPs) cause inhibition of the K+/Cl- cotransporter (a transporter mediating RVD), whilst some inhibitors of protein kinases (PKs) cause activation. A sequence of potential phosphorylation sites appears to constitute a cascade of reactions leading to transporter regulation. PP and PK inhibitors have opposite effects on transporters mediating RVI responses, which is consistent with the coordinated but reciprocal regulation of transporters activated during both RVI and RVD using some common phosphorylation reactions. The transporters are sensitive to other stimuli including, in red blood cells, changes in PO2 and pH. These responses are also sensitive to PK/PP inhibitors and may involve elements of the volume-sensitive transduction pathway.