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. 1989 Jul;84(1):352–356. doi: 10.1172/JCI114162

Guanine nucleotide-binding protein, alpha i-3, directly activates a cation channel in rat renal inner medullary collecting duct cells.

D B Light 1, D A Ausiello 1, B A Stanton 1
PMCID: PMC303990  PMID: 2472428

Abstract

We examined whether GTP binding proteins (G proteins) regulate sodium conducting channels in the apical membrane of renal inner medullary collecting duct (IMCD) cells and thereby modulate sodium absorption. Patch clamp studies were conducted on inside-out patches of the apical membrane of IMCD cells grown in primary culture. Guanosine 5'-triphosphate (GTP) and the nonhydrolyzable GTP analogue, GTP gamma S, which activate G proteins, increased the open probability of the cation channel. In contrast, the nonhydrolyzable GDP analogue, GDP beta S, which decreases G protein activity, inhibited the channel. Pertussis toxin also reduced the open probability of the channel. Addition of the alpha *i-3 subunit of Gi to the solution bathing the cytoplasmic surface of the membrane increased the open probability in a dose-dependent manner (2-200 pM). The threshold concentration for activation by alpha *i-3 was 2 pM. Activation of the cation channel by alpha *i-3 was not mediated via a protein kinase. The IMCD is the first polarized epithelium in which an ion channel has been shown to be directly regulated by a G protein. Thus, G proteins are important elements in regulating sodium absorption by the IMCD.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bourne H. R. G-protein subunits. Who carries what message? Nature. 1989 Feb 9;337(6207):504–504. doi: 10.1038/337504a0. [DOI] [PubMed] [Google Scholar]
  2. Brown A. M., Birnbaumer L. Direct G protein gating of ion channels. Am J Physiol. 1988 Mar;254(3 Pt 2):H401–H410. doi: 10.1152/ajpheart.1988.254.3.H401. [DOI] [PubMed] [Google Scholar]
  3. Cerbai E., Klöckner U., Isenberg G. The alpha subunit of the GTP binding protein activates muscarinic potassium channels of the atrium. Science. 1988 Jun 24;240(4860):1782–1783. doi: 10.1126/science.2454511. [DOI] [PubMed] [Google Scholar]
  4. Codina J., Grenet D., Yatani A., Birnbaumer L., Brown A. M. Hormonal regulation of pituitary GH3 cell K+ channels by Gk is mediated by its alpha-subunit. FEBS Lett. 1987 May 25;216(1):104–106. doi: 10.1016/0014-5793(87)80765-2. [DOI] [PubMed] [Google Scholar]
  5. Codina J., Yatani A., Grenet D., Brown A. M., Birnbaumer L. The alpha subunit of the GTP binding protein Gk opens atrial potassium channels. Science. 1987 Apr 24;236(4800):442–445. doi: 10.1126/science.2436299. [DOI] [PubMed] [Google Scholar]
  6. Fain J. N., Wallace M. A., Wojcikiewicz R. J. Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones. FASEB J. 1988 Jul;2(10):2569–2574. doi: 10.1096/fasebj.2.10.2838362. [DOI] [PubMed] [Google Scholar]
  7. Frindt G., Palmer L. G. Ca-activated K channels in apical membrane of mammalian CCT, and their role in K secretion. Am J Physiol. 1987 Mar;252(3 Pt 2):F458–F467. doi: 10.1152/ajprenal.1987.252.3.F458. [DOI] [PubMed] [Google Scholar]
  8. Hescheler J., Rosenthal W., Trautwein W., Schultz G. The GTP-binding protein, Go, regulates neuronal calcium channels. 1987 Jan 29-Feb 4Nature. 325(6103):445–447. doi: 10.1038/325445a0. [DOI] [PubMed] [Google Scholar]
  9. Katada T., Gilman A. G., Watanabe Y., Bauer S., Jakobs K. H. Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem. 1985 Sep 2;151(2):431–437. doi: 10.1111/j.1432-1033.1985.tb09120.x. [DOI] [PubMed] [Google Scholar]
  10. Kim D., Lewis D. L., Graziadei L., Neer E. J., Bar-Sagi D., Clapham D. E. G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Nature. 1989 Feb 9;337(6207):557–560. doi: 10.1038/337557a0. [DOI] [PubMed] [Google Scholar]
  11. Kurachi Y., Ito H., Sugimoto T., Katada T., Ui M. Activation of atrial muscarinic K+ channels by low concentrations of beta gamma subunits of rat brain G protein. Pflugers Arch. 1989 Jan;413(3):325–327. doi: 10.1007/BF00583550. [DOI] [PubMed] [Google Scholar]
  12. Kurachi Y., Ito H., Sugimoto T., Shimizu T., Miki I., Ui M. Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel. Nature. 1989 Feb 9;337(6207):555–557. doi: 10.1038/337555a0. [DOI] [PubMed] [Google Scholar]
  13. Light D. B., McCann F. V., Keller T. M., Stanton B. A. Amiloride-sensitive cation channel in apical membrane of inner medullary collecting duct. Am J Physiol. 1988 Aug;255(2 Pt 2):F278–F286. doi: 10.1152/ajprenal.1988.255.2.F278. [DOI] [PubMed] [Google Scholar]
  14. Light D. B., Schwiebert E. M., Karlson K. H., Stanton B. A. Atrial natriuretic peptide inhibits a cation channel in renal inner medullary collecting duct cells. Science. 1989 Jan 20;243(4889):383–385. doi: 10.1126/science.2463673. [DOI] [PubMed] [Google Scholar]
  15. Logothetis D. E., Kurachi Y., Galper J., Neer E. J., Clapham D. E. The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature. 1987 Jan 22;325(6102):321–326. doi: 10.1038/325321a0. [DOI] [PubMed] [Google Scholar]
  16. Mohrmann M., Cantiello H. F., Ausiello D. A. Inhibition of epithelial Na+ transport by atriopeptin, protein kinase c, and pertussis toxin. Am J Physiol. 1987 Aug;253(2 Pt 2):F372–F376. doi: 10.1152/ajprenal.1987.253.2.F372. [DOI] [PubMed] [Google Scholar]
  17. Ribeiro-Neto F. A., Mattera R., Hildebrandt J. D., Codina J., Field J. B., Birnbaumer L., Sekura R. D. ADP-ribosylation of membrane components by pertussis and cholera toxin. Methods Enzymol. 1985;109:566–572. doi: 10.1016/0076-6879(85)09115-7. [DOI] [PubMed] [Google Scholar]
  18. Scott R. H., Dolphin A. C. Activation of a G protein promotes agonist responses to calcium channel ligands. Nature. 1987 Dec 24;330(6150):760–762. doi: 10.1038/330760a0. [DOI] [PubMed] [Google Scholar]
  19. Stanton B. A. Characterization of apical and basolateral membrane conductances of rat inner medullary collecting duct. Am J Physiol. 1989 May;256(5 Pt 2):F862–F868. doi: 10.1152/ajprenal.1989.256.5.F862. [DOI] [PubMed] [Google Scholar]
  20. Stokes J. B., Grupp C., Kinne R. K. Purification of rat papillary collecting duct cells: functional and metabolic assessment. Am J Physiol. 1987 Aug;253(2 Pt 2):F251–F262. doi: 10.1152/ajprenal.1987.253.2.F251. [DOI] [PubMed] [Google Scholar]
  21. VanDongen A. M., Codina J., Olate J., Mattera R., Joho R., Birnbaumer L., Brown A. M. Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go. Science. 1988 Dec 9;242(4884):1433–1437. doi: 10.1126/science.3144040. [DOI] [PubMed] [Google Scholar]
  22. Yanase M., Handler J. S. Activators of protein kinase C inhibit sodium transport in A6 epithelia. Am J Physiol. 1986 Mar;250(3 Pt 1):C517–C522. doi: 10.1152/ajpcell.1986.250.3.C517. [DOI] [PubMed] [Google Scholar]
  23. Yatani A., Codina J., Brown A. M., Birnbaumer L. Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk. Science. 1987 Jan 9;235(4785):207–211. doi: 10.1126/science.2432660. [DOI] [PubMed] [Google Scholar]
  24. Yatani A., Codina J., Imoto Y., Reeves J. P., Birnbaumer L., Brown A. M. A G protein directly regulates mammalian cardiac calcium channels. Science. 1987 Nov 27;238(4831):1288–1292. doi: 10.1126/science.2446390. [DOI] [PubMed] [Google Scholar]
  25. Yatani A., Codina J., Sekura R. D., Birnbaumer L., Brown A. M. Reconstitution of somatostatin and muscarinic receptor mediated stimulation of K+ channels by isolated GK protein in clonal rat anterior pituitary cell membranes. Mol Endocrinol. 1987 Apr;1(4):283–289. doi: 10.1210/mend-1-4-283. [DOI] [PubMed] [Google Scholar]
  26. Yatani A., Hamm H., Codina J., Mazzoni M. R., Birnbaumer L., Brown A. M. A monoclonal antibody to the alpha subunit of Gk blocks muscarinic activation of atrial K+ channels. Science. 1988 Aug 12;241(4867):828–831. doi: 10.1126/science.2457252. [DOI] [PubMed] [Google Scholar]
  27. Zick Y., Sagi-Eisenberg R., Pines M., Gierschik P., Spiegel A. M. Multisite phosphorylation of the alpha subunit of transducin by the insulin receptor kinase and protein kinase C. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9294–9297. doi: 10.1073/pnas.83.24.9294. [DOI] [PMC free article] [PubMed] [Google Scholar]

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