Volume-regulatory K+ fluxes in the isolated perfused rat liver: characterization by ion transport inhibitors

Net hepatic release and uptake of K+ were examined in isolated perfused rat livers subjected to a 10-min period of hypotonic stress. Effluent Na+, K+, and Ca2+ activities were monitored throughout. Initiation and termination of hypotonic stress triggered sharp transient (less than 1 min) changes in effluent ion activities that indicated net water movement into and out of the liver, respectively. In addition, hypotonic stress caused a large transient net release of hepatic K+, whereas return to isotonicity triggered a transient net hepatic K+ uptake. The hypotonically induced K+ release was inhibited by 2 mM barium (95%) and by 1 mM quinine (60%). Net K+ influx, on the other hand, was inhibited by 1 mM ouabain (100%) and by 1 mM amiloride (50%). Osmotically induced K+ fluxes were not significantly affected by bicarbonate removal and were only partially inhibited by 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or bumetanide. The results suggest that K+ conductance increases during hypotonic stress, whereas return to isotonicity induces a ouabain-sensitive K+ uptake partly because of increased Na+-H+ exchange. These mechanisms probably participate in regulatory volume decrease and regulatory volume increase, respectively.