NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+-K+-ATPase.
Background: In K+ deprivation (KD), gastric (g) H+-K+-ATPase (HKA) is suppressed, whereas colonic (c) HKA is induced in the terminal inner medullary collecting duct (IMCD). We hypothesized that in KD, cHKA is induced and can mediate the secretion of NH4+.
Methods: Rats were sacrificed after 2, 3, 6, or 14 days on regular (NML) or K+-free (KD) diet. mRNA expression of HKA isoforms in terminal inner medulla was examined and correlated with NH4+ secretion in perfused IMCD in vitro.
Results: Urinary NH4+ excretion increased after K+-free diet for six days. In terminal inner medulla, cHKA expression was strongly induced, whereas gHKA expression was decreased. NH4+ secretion increased by 62% in KD (JtNH4+ 0.57 vs. 0.92 pmol/min/mm tubule length, P < 0.001). Ouabain (1 mM) in perfusate inhibited NH4+ secretion in KD by 45% (P < 0.002) but not in NML. At luminal pH 7.7, which inhibits NH3 diffusion, NH4+ secretion in IMCD was 140% higher in KD (0.36 vs. 0.15, P < 0.03) and was sensitive to ouabain. ROMK-1 mRNA expression was induced in parallel with cHKA in inner medulla.
Conclusions: These data suggest that in KD, cHKA replaces gHKA and mediates enhanced secretion of NH4+ (and H+) into the lumen facilitated by K+ recycling through ROMK-1.