VOLUME REGULATION IN NIH 3T3 CELLS NOT EXPRESSING P-GLYCOPROTEIN .1. REGULATORY VOLUME DECREASE/

Exposure of NIH/3T3 fibroblasts not expressing P-glycoprotein to 50, 3 0, 20, and 10% hyposmotic solutions led to cell volume increases of 70 , 32, 21, and 12%, respectively. After swelling, NIH/3T3 cells exhibit ed regulatory volume decrease (RVD), attaining complete volume recover y after 30 min except in 50% hyposmotic solution, in which volume reco very was 76%. RVD was accelerated by gramicidin and inhibited by the C l channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, 1,9-di deoxyforskolin, dipyridamole, and niflumic acid and by the K channel b locker quinidine. RVD was reduced 15% by removal of extracellular Ca. The pathway opened by hypotonicity was highly permeable to K and Rb an d only partly permeable to other cations. Most anions were able to per meate, with a permeability ranking of nitrate > benzoate = iodide > th iocyanate > chloride much greater than gluconate. The pathway was perm eable to neutral amino acids, with a permeability ranking of glycine > alanine > glutamate > taurine > gamma-aminobutyric acid > glutamine. The pathway was not permeable to basic amino acids. These results show that, despite the absence of P-glycoprotein, NIH/3T3 cells exhibit RV D with properties similar to those expressed in most cell types.