1. 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) m
ol l-1 (mean +/- S.D., n = 4). Conversely, RVD was resistant to quinin
e, quinidine, apamin, cetiedil, amiloride, bumetanide and DIDS (4,4'-d
iisothiocyanostilbene-2,2'-disulphonate). 2. DIOA-sensitive RVD follow
ed mono-exponential kinetics, with t1/2 (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. 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 unabl
e to accelerate RVD or RVD reversal. 5. In the presence of DIOA, thymo
cytes responded like osmometers (the relative cell volume was a linear
function of the reciprocal of the relative osmolality) in a large ran
ge of osmolalities. 6. The results strongly suggest that RVD in rat th
ymocytes is mediated by the K+-Cl- co-transport system.