CLONING, EXPRESSION, AND TISSUE DISTRIBUTION OF A HUMAN AMILORIDE-SENSITIVE NA+ CHANNEL

被引:196
作者
MCDONALD, FJ
SNYDER, PM
MCCRAY, PB
WELSH, MJ
机构
[1] UNIV IOWA,COLL MED,HOWARD HUGHES MED INST,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242
[2] UNIV IOWA,COLL MED,HOWARD HUGHES MED INST,DEPT PEDIAT,IOWA CITY,IA 52242
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1994年 / 266卷 / 06期
关键词
EPITHELIA; DEGENERINS; COMPLEMENTARY DEOXYRIBONUCLEIC ACID; LUNG; ABSORPTION;
D O I
10.1152/ajplung.1994.266.6.L728
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Amiloride-sensitive Na+ channels control, in part, fluid and electrolyte transport across epithelia in many organs. In the lung, they control the quantity and composition of the respiratory tract fluid and play a key role in the transition from a fluid-filled lung at the time of birth. Their function may also be altered in a number of diseases. The recent identification of an epithelial Na+ channel from rat colon allowed us to use a probe from that sequence to clone an amiloride-sensitive Na+ channel from human kidney, alpha hENaC. The cDNA had an open reading frame of 2,007 nucleotides and encoded a protein predicted to contain 669 amino acids. The amino acid sequence of alpha hENaC was 83% identical to that of the rat. The gene was mapped to chromosome 12 by polymerase chain reaction (PCR) of somatic cell hybrids. Transcripts of alpha hENaC were detected in human kidney, lung, liver, and pancreas. No message was detected in first- and second-trimester human fetal lung, indicating that alpha hENaC expression is developmentally regulated. In vitro transcription and translation of alpha hENaC produced a 74-kDa protein and translation in the presence of microsomal membranes produced a glycosylated 87-kDa protein. Expression of alpha hENaC in Xenopus oocytes produced currents that were amiloride sensitive and Na+ selective, properties consistent with the function of epithelial Na+ channels in native tissues.
引用
收藏
页码:L728 / L734
页数:7
相关论文
共 33 条
  • [1] A TRANSIENT CALCIUM-DEPENDENT CHLORIDE CURRENT IN THE IMMATURE XENOPUS OOCYTE
    BARISH, ME
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1983, 342 (SEP): : 309 - 325
  • [2] BENOS DJ, 1987, J BIOL CHEM, V262, P10613
  • [3] LIDDLES SYNDROME REVISITED - A DISORDER OF SODIUM-REABSORPTION IN THE DISTAL TUBULE
    BOTEROVELEZ, M
    CURTIS, JJ
    WARNOCK, DG
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (03) : 178 - 181
  • [4] NA+ TRANSPORT IN CYSTIC-FIBROSIS RESPIRATORY EPITHELIA - ABNORMAL BASAL RATE AND RESPONSE TO ADENYLATE-CYCLASE ACTIVATION
    BOUCHER, RC
    STUTTS, MJ
    KNOWLES, MR
    CANTLEY, L
    GATZY, JT
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (05) : 1245 - 1252
  • [5] EPITHELIAL SODIUM-CHANNEL RELATED TO PROTEINS INVOLVED IN NEURODEGENERATION
    CANESSA, CM
    HORISBERGER, JD
    ROSSIER, BC
    [J]. NATURE, 1993, 361 (6411) : 467 - 470
  • [6] CESTARI IN, 1993, BIOTECHNIQUES, V14, P404
  • [7] THE IDENTIFICATION AND SUPPRESSION OF INHERITED NEURODEGENERATION IN CAENORHABDITIS-ELEGANS
    CHALFIE, M
    WOLINSKY, E
    [J]. NATURE, 1990, 345 (6274) : 410 - 416
  • [8] DEGENERIN SIMILARITIES
    CHALFIE, M
    DRISCOLL, M
    HUANG, MX
    [J]. NATURE, 1993, 361 (6412) : 504 - 504
  • [9] CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
  • [10] GENOMIC SEQUENCING
    CHURCH, GM
    GILBERT, W
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (07): : 1991 - 1995