Expression of HKα 2 protein is increased selectively in renal medulla by chronic hypokalemia

• Published in: American journal of physiology. Renal physiology Vol. 275; no. 3; pp. F433 - F440
• Main Authors: Codina, Juan, Delmas-Mata, Juan T, DuBose, Jr, Thomas D
• Format: Journal Article
• Language: English
• Published: United States 01.09.1998
• Subjects: urinary acidification; proton-potassium-adenosinetriphosphatase; acidosis; distal colon
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.1998.275.3.F433

Our laboratory has demonstrated by Northern analysis that chronic hypokalemia increases HKα (i.e., α-subunit of the colonic H -K -ATPase) mRNA abundance in the rat. To determine whether the increase in mRNA correlated with an increase in HKα protein, an antibody was raised against a synthetic peptide derived from amino acids 686-698 of the HKα sequence. The anti-HKα antibody hybridized to rat distal colon membranes which migrated at ∼100 kDa (expected mobility of HKα ). HKα protein was not detected in plasma membranes from rat whole kidney or stomach (100 μg) derived from control animals. The antibody was then used to investigate changes in expression of HKα in renal cortex, renal medulla, and distal colon in two pathophysiological conditions: 1) chronic hypokalemia (LK) and 2) chronic metabolic acidosis (CMA). In LK rats there was a marked, but selective, increase in the abundance of HKα protein in membranes prepared from renal medulla. Nevertheless, a corresponding increase in HKα protein abundance was not observed in membranes prepared from the distal colon of LK rats. HKα protein abundance in CMA was indistinguishable from controls. Moreover, chronic hypokalemia had no effect on expression of α -Na -K -ATPase or HKα in kidney or distal colon under any experimental condition. Therefore, HKα protein is tissue- and site-specifically upregulated in response to chronic hypokalemia but not by CMA. Furthermore, this regulatory response is localized to the renal medulla.