VOLUME-SENSITIVE TRANSPORT-SYSTEMS AND VOLUME HOMEOSTASIS IN VERTEBRATE RED-BLOOD-CELLS

Animal cells regulate their volume in the short term by controlling so lute movements into and out of the cell. A suite of dissipative transp ort 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 stu dies have identified transmembrane transport domains and cytoplasmic r egulatory domains, In vertebrate red blood cells, protein phosphorylat ion appears to be central to the coordinated regulation of transporter activity. Inhibitors of protein phosphatases (PPs) cause inhibition o f the K+/Cl- cotransporter (a transporter mediating RVD), whilst some inhibitors of protein kinases (PKs) cause activation. A sequence of po tential phosphorylation sites appears to constitute a cascade of react ions leading to transporter regulation, PP and PK inhibitors have oppo site effects on transporters mediating RVI responses, which is consist ent with the coordinated but reciprocal regulation of transporters act ivated during both RVI and RVD using some common phosphorylation react ions, The transporters are sensitive to other stimuli including, in re d blood cells, changes in P-O2 and pH. These responses are also sensit ive to PK/PP inhibitors and may involve elements of the volume-sensiti ve transduction pathway.