Renal H,K-ATPase: structure, function and regulation.

B C Kone

Home/Archive/PubMed

PubMed · 8933506

Renal H,K-ATPase: structure, function and regulation.

B C Kone

View original source ↗Export metadata ↓

Abstract

The H,K-ATPase comprises a family of isoenzymes with unique biochemical, pharmacological, and regulatory properties. This review explores recent advances in discovery of the molecular biology, biochemistry, and function of these ion pumps, with particular emphasis on the implications for renal potassium and proton handling. Structure-function correlations governing the ion transport mechanisms, inhibitor binding sites, oligomerization, and transcriptional control of the H,K-ATPase isoforms are examined. Functional studies of H,K-ATPase in renal tubules and cultured epithelial cells are analyzed and related to data concerning the expression and distribution of the H,K-ATPase gene products in the kidney. Functional and molecular biological evidence for adaptive changes in renal H,K-ATPase expression during the evolution of potassium and acid-base disturbances are discussed. Current investigative challenges and avenues for future research of these enzymes are presented.

Explore related subjects

Acid-Base Imbalance Amino Acid Sequence Animals Binding Sites Cell Membrane H(+)-K(+)-Exchanging ATPase Isoenzymes Kidney Molecular Sequence Data Potassium Structure-Activity Relationship Transcription, Genetic Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

B C Kone. 1996. Renal H,K-ATPase: structure, function and regulation.. https://pubmed.ncbi.nlm.nih.gov/8933506/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Unmeasured anions in children after cardiac surgery.

OBJECTIVES: Acidosis caused by increased unmeasured anion levels occurs frequently after cardiac surgery, with uncertain significance. We examined the ability of unmeasured anions and lactate to predict major events after cardiac surgery, in addition to lactate/increased unmeasured anion levels during low cardiac output states. METHODS: In the initial 6 months, all patients admitted after cardiac surgery were enrolled. Arterial samples were taken at 0, 4, 8, 12, 24, and 36 hours postoperatively. The Stewart method was used to calculate excess acid and unmeasured anion levels. Major adverse events were defined as low cardiac output states requiring cardiac massage or mechanical support. In the second 6-month period, data were collected from a further 8 infants during cardiac arrest/extracorporeal membrane oxygenation cannulation. RESULTS: One hundred thirteen patients were analyzed. Major adverse events occurred in 8 (7.1%) of 113 patients. On admission, metabolic acidosis occurred in 94 of 113 samples: lactate alone (n = 25); mixed lactate and unmeasured anions (n = 44); and unmeasured anions alone (n = 25). All of the patients who experienced major adverse events had unmeasured anion levels of greater than 3 mEq/L on admission. Initial unmeasured anion levels were significantly higher in those infants with major adverse events (10.6 mEq/L [standard deviation, 8.2 mEq/L] vs 4.8 mEq/L [standard deviation, 6.6 mEq/L], P = .024). Lactate levels did not differ between the 2 groups. In the 16 patients sampled during major adverse events, metabolic acidosis occurred in 15 of 16, with a mean excess acid level of 14.9 mEq/L (standard deviation, 8.3 mEq/L). Although unmeasured anions made a significant contribution, lactate was the predominant acid. CONCLUSIONS: After cardiac surgery, unmeasured anion levels were significantly higher in those children with major adverse events. The greatest risk of major adverse events was found in children with both increased lactate levels and increased unmeasured anion levels on admission.

Acid-Base Imbalance↗

PubMed2006

Distinctive acid-base pattern in Wernicke's encephalopathy.

Wernicke's encephalopathy may result in severe morbidity and possible mortality when unrecognized. We report a distinctive acid-base pattern that has not been associated with this syndrome. This is a case series of patients with Wernicke's encephalopathy who had an arterial blood gas measurement performed on initial presentation. Exclusion criteria were patients with an unclear diagnosis of Wernicke's encephalopathy and those for whom no arterial blood gas measurement was performed. Four patients with Wernicke's encephalopathy were included in the analysis. All 4 patients exhibited an anion-gap (primary) metabolic acidosis, accompanied by a primary respiratory alkalosis. Three of 4 patients exhibited a significant lactic acidosis. None of the patients had any competing diagnoses or dysfunction to account for this acid-base pattern. Patients with Wernicke's encephalopathy may exhibit a distinctive acid-base pattern consisting of a primary metabolic acidosis in conjunction with a primary respiratory alkalosis. Observation of this acid-base disturbance should prompt clinicians to consider thiamine deficiency disorders as a possible cause.

Acid-Base Imbalance↗

PubMed2006

Regulation of kidney acid excretion by endothelins.

Endothelin (ET) is a potent vasoconstrictor that is now known to modulate kidney tubule transport, including kidney tubule acidification. Animals undergoing an acid challenge to systemic acid-base status and with some models of chronic metabolic acidosis have increased kidney ET production. Increased ET production/activity contributes to enhanced kidney tubule acidification that facilitates kidney acid excretion in response to an acid challenge to systemic acid-base status. The data to date support a physiologic role for ET in mediating enhanced kidney acidification in response to acid challenges, but do not support an ET role in maintaining kidney tubule acidification in control, non-acid-challenged states. ET increases acidification in both the proximal and distal nephron and appears to exert its effects both directly and indirectly, the latter through modulating the levels and/or activity or other mediators of kidney tubule acidification. ET also contributes to enhanced kidney acidification in some pathophysiologic states and might contribute to some untoward outcomes associated with these conditions. Whether ET should be a therapeutic target in treating and/or preventing some of these untoward outcomes remains an open question. This review supports continued research into the physiologic and possibly pathophysiologic role of ET in settings of increased kidney tubule acidification.

Acid-Base Imbalance↗