K+/Na+ antagonism at cytoplasmic sites of Na+-K+-ATPase:: a tissue-specific mechanism of sodium pump regulation

被引:36
作者
Therien, AG [1 ]
Blostein, R [1 ]
机构
[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1A4, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1999年 / 277卷 / 05期
关键词
alpha(1)-isoform; heart; kidney;
D O I
10.1152/ajpcell.1999.277.5.C891
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 approximate to 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 greater than or equal to kidney > small intestine approximate to 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.
引用
收藏
页码:C891 / C898
页数:8
相关论文
共 31 条
[1]   INFLUENCE OF CALCIUM ON SODIUM EFFLUX IN SQUID AXONS [J].
BAKER, PF ;
BLAUSTEIN, MP ;
HODGKIN, AL ;
STEINHARDT, RA .
JOURNAL OF PHYSIOLOGY-LONDON, 1969, 200 (02) :431-+
[2]   SHORT-TERM REGULATION OF RENAL NA-K-ATPASE ACTIVITY - PHYSIOLOGICAL RELEVANCE AND CELLULAR MECHANISMS [J].
BERTORELLO, AM ;
KATZ, AI .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 265 (06) :F743-F755
[3]   Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function [J].
Blanco, G ;
Mercer, RW .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1998, 275 (05) :F633-F650
[4]  
CHOW DC, 1995, J EXP BIOL, V198, P1
[5]  
CROWSON MS, 1992, J BIOL CHEM, V267, P13740
[6]   Structure/function analysis of the amino-terminal region of the alpha 1 and alpha 2 subunits of Na,K-ATPase [J].
Daly, SE ;
Lane, LK ;
Blostein, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (39) :23683-23689
[7]  
Doucet A, 1985, Adv Nephrol Necker Hosp, V14, P87
[8]   HORMONAL-REGULATION OF THE NA+-K+-ATPASE - MECHANISMS UNDERLYING RAPID AND SUSTAINED CHANGES IN PUMP ACTIVITY [J].
EWART, HS ;
KLIP, A .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1995, 269 (02) :C295-C311
[9]   INTESTINAL ION-TRANSPORT AND DIARRHEAL DISEASE [J].
FONDACARO, JD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 250 (01) :G1-G8