DIOA (dihydroindenyl-oxy-alkanoic acid), a potent inhibitor of the K+-CI- cotransport system, fully blocked regulatory volume decrease (RVD) in swelled rat thymocytes, with an IC50 of 2.2±0.5x10-5 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). DIOA-sensitive RVD followed mono-exponential kinetics, with t( 1/2 ) (half-lifetime) of 1-3 min and maximal capacity (C(max)) of about 55% of the initial cell swelling. C(max); and the initial rate of RVD (V(o)) were both linear functions of the increase in cell volume. 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 μmol l-1). Increased membrane potassium permeability by valinomycin was unable to accelerate RVD or RVD reversal. 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. The results strongly suggest that RVD in rat thymocytes is mediated by the K+-Cl- co-transport system.
|Number of pages||12|
|Journal||Journal of Physiology|
|Publication status||Published - 1993|
ASJC Scopus subject areas