DIOA (dihydroindenyl-oxy-alkanoic acid), a potent inhibitor of the K(+)-Cl- co-transport system, fully blocked regulatory volume decrease (RVD) in swelled rat thymocytes, with an IC50 of 2.2 +/- 0.5 x 10(-5) mol l-1 (mean +/- S.D., n = 4). Conversely, RVD was resistant to quinine, quinidine, apamin, cetiedil, amiloride, bumetanide and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonate). 2. DIOA-sensitive RVD followed mono-exponential kinetics, with t1/2 (half-lifetime) of 1-3 min and maximal capacity (Cmax) of about 55% of the initial cell swelling. Cmax and the initial rate of RVD (Vo) were both linear functions of the increase in cell volume. 3. RVD was: (i) slightly increased by replacing external Cl- by NO3-, (ii) reversed by replacing external Na+ by K+ (in the presence of external Cl-) and (iii) inhibited by cell K+ depletion. All these phenomena were blocked by DIOA (86 mumol l-1). 4. Increased membrane potassium permeability by valinomycin was unable to accelerate RVD or RVD reversal. 5. In the presence of DIOA, thymocytes responded like osmometers (the relative cell volume was a linear function of the reciprocal of the relative osmolality) in a large range of osmolalities. 6. The results strongly suggest that RVD in rat thymocytes is mediated by the K(+)-Cl- co-transport system.
