title: K(+)/Na(+) antagonism at cytoplasmic sites of Na(+)-K(+)-ATPase: a tissue-specific mechanism of sodium pump regulation.
abstract: Tissue-distinct interactions of the Na(+)-K(+)-ATPase with Na(+) and K(+), independent of isoform-specific properties, were reported previously (A. G. Therien, N. B. Nestor, W. J. Ball, and R. Blostein. J. Biol. Chem. 271: 7104-7112, 1996). In this paper, we describe a detailed analysis of tissue-specific kinetics particularly relevant to regulation of pump activity by intracellular K(+), namely K(+) inhibition at cytoplasmic Na(+) sites. Our results show that the order of susceptibilities of alpha(1) pumps of various rat tissues to K(+)/Na(+) antagonism, represented by the ratio of the apparent affinity for Na(+) binding at cytoplasmic activation sites in the absence of K(+) to the affinity constant for K(+) as a competitive inhibitor of Na(+) binding at cytoplasmic sites, is red blood cell < axolemma approximately rat alpha(1)-transfected HeLa cells < small intestine < kidney < heart. In addition, we have carried out an extensive analysis of the kinetics of K(+) binding and occlusion to the cytoplasmic cation binding site and find that, for most tissues, there is a relationship between the rate of K(+) binding/occlusion and the apparent affinity for K(+) as a competitive inhibitor of Na(+) activation, the order for both parameters being heart >/= kidney > small intestine approximately rat alpha(1)-transfected HeLa cells. The notion that modulations in cytoplasmic K(+)/Na(+) antagonism are a potential mode of pump regulation is underscored by evidence of its reversibility. Thus the relatively high K(+)/Na(+) antagonism characteristic of kidney pumps was reduced when rat kidney microsomal membranes were fused into the dog red blood cell.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Canada H3G 1A4.
authors.forename: A G
authors.initials: AG
authors.lastname: Therien
authors.forename: R
authors.initials: R
authors.lastname: Blostein
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002459:Cell Fusion; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000737:chemistry / Q000201:enzymology*; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D007421:Intestine, Small / Q000166:cytology; D007679:Kidney Medulla / Q000166:cytology; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D008861:Microsomes / Q000737:chemistry / Q000201:enzymology; D009206:Myocardium / Q000166:cytology; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism*; D011189:Potassium Chloride / Q000493:pharmacokinetics; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D012965:Sodium Chloride / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D012965:Sodium Chloride; D011189:Potassium Chloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium