In hepatocytes in vitro, Na+/H+ exchange, an important regulator of intracellular pH, is activated by epidermal growth factor, but its activity during liver regeneration in vivo is unknown. We therefore compared activity and regulation of Na+/H+ exchange in hepatocytes isolated after two-thirds partial hepatectomy or sham surgery, respectively, by measuring intracellular pH (fluorimetry) and steady state Na+/H+ exchange mRNA levels (Northern blotting). Resting intracellular pH increased from 7.06 +/- 0.02 to 7.12 +/- 0.02 (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Na+/H+ exchange-mediated rates of intracellular pH recovery from an acid load increased from 0.075 +/- 0.018 to 0.151 +/- 0.018 pH units/min (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Because intracellular buffering capacity was not affected, this reflects increased Na+/H+ exchange activity. The inverse relationship between Na+/H+ exchange activity and intracellular pH was shifted by about 0.1 pH units toward more alkaline pH values 2 hr but not 20 hr after partial hepatectomy, whereas steady-state Na+/H+ exchange mRNA levels remained unchanged. In conclusion, hepatocellular Na+/H+ exchange is activated early, transiently and at a posttranscriptional level during liver regeneration induced in the rat by partial hepatectomy.

No abstract