Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jul 3;92(14):6542–6546. doi: 10.1073/pnas.92.14.6542

Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers.

P Kofuji 1, N Davidson 1, H A Lester 1
PMCID: PMC41554  PMID: 7604029

Abstract

Guanine nucleotide-binding proteins (G proteins) activate K+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a G-protein-coupled, inwardly rectifying K+ channel (GIRK) have recently been cloned from cardiac (GIRK1/Kir 3.1) and brain cDNA libraries (GIRK2/Kir 3.2 and GIRK3/Kir 3.3). Here we report that GIRK2 but not GIRK3 can be activated by G protein subunits G beta 1 and G gamma 2 in Xenopus oocytes. Furthermore, when either GIRK3 or GIRK2 was coexpressed with GIRK1 and activated either by muscarinic receptors or by G beta gamma subunits, G-protein-mediated inward currents were increased by 5- to 40-fold. The single-channel conductance for GIRK1 plus GIRK2 coexpression was intermediate between those for GIRK1 alone and for GIRK2 alone, and voltage-jump kinetics for the coexpressed channels displayed new kinetic properties. On the other hand, coexpression of GIRK3 with GIRK2 suppressed the GIRK2 alone response. These studies suggest that formation of heteromultimers involving the several GIRKs is an important mechanism for generating diversity in expression level and function of neurotransmitter-coupled, inward rectifier K+ channels.

Full text

PDF
6542

Selected References

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

  1. Andrade R., Malenka R. C., Nicoll R. A. A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science. 1986 Dec 5;234(4781):1261–1265. doi: 10.1126/science.2430334. [DOI] [PubMed] [Google Scholar]
  2. Ashford M. L., Bond C. T., Blair T. A., Adelman J. P. Cloning and functional expression of a rat heart KATP channel. Nature. 1994 Aug 11;370(6489):456–459. doi: 10.1038/370456a0. [DOI] [PubMed] [Google Scholar]
  3. Bradley J., Li J., Davidson N., Lester H. A., Zinn K. Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8890–8894. doi: 10.1073/pnas.91.19.8890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Canessa C. M., Schild L., Buell G., Thorens B., Gautschi I., Horisberger J. D., Rossier B. C. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994 Feb 3;367(6462):463–467. doi: 10.1038/367463a0. [DOI] [PubMed] [Google Scholar]
  5. Chen T. Y., Peng Y. W., Dhallan R. S., Ahamed B., Reed R. R., Yau K. W. A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature. 1993 Apr 22;362(6422):764–767. doi: 10.1038/362764a0. [DOI] [PubMed] [Google Scholar]
  6. Clapham D. E. Direct G protein activation of ion channels? Annu Rev Neurosci. 1994;17:441–464. doi: 10.1146/annurev.ne.17.030194.002301. [DOI] [PubMed] [Google Scholar]
  7. Dascal N., Schreibmayer W., Lim N. F., Wang W., Chavkin C., DiMagno L., Labarca C., Kieffer B. L., Gaveriaux-Ruff C., Trollinger D. Atrial G protein-activated K+ channel: expression cloning and molecular properties. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10235–10239. doi: 10.1073/pnas.90.21.10235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DePaoli A. M., Bell G. I., Stoffel M. G protein-activated inwardly rectifying potassium channel (GIRK1/KGA) mRNA in adult rat heart and brain by in situ hybridization histochemistry. Mol Cell Neurosci. 1994 Dec;5(6):515–522. doi: 10.1006/mcne.1994.1063. [DOI] [PubMed] [Google Scholar]
  9. Hille B. G protein-coupled mechanisms and nervous signaling. Neuron. 1992 Aug;9(2):187–195. doi: 10.1016/0896-6273(92)90158-a. [DOI] [PubMed] [Google Scholar]
  10. Inoue M., Nakajima S., Nakajima Y. Somatostatin induces an inward rectification in rat locus coeruleus neurones through a pertussis toxin-sensitive mechanism. J Physiol. 1988 Dec;407:177–198. doi: 10.1113/jphysiol.1988.sp017409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kain K. C., Orlandi P. A., Lanar D. E. Universal promoter for gene expression without cloning: expression-PCR. Biotechniques. 1991 Mar;10(3):366–374. [PubMed] [Google Scholar]
  12. Karschin A., Ho B. Y., Labarca C., Elroy-Stein O., Moss B., Davidson N., Lester H. A. Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5694–5698. doi: 10.1073/pnas.88.13.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Krapivinsky G., Gordon E. A., Wickman K., Velimirović B., Krapivinsky L., Clapham D. E. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. Nature. 1995 Mar 9;374(6518):135–141. doi: 10.1038/374135a0. [DOI] [PubMed] [Google Scholar]
  14. Kubo Y., Reuveny E., Slesinger P. A., Jan Y. N., Jan L. Y. Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel. Nature. 1993 Aug 26;364(6440):802–806. doi: 10.1038/364802a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Lesage F., Duprat F., Fink M., Guillemare E., Coppola T., Lazdunski M., Hugnot J. P. Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain. FEBS Lett. 1994 Oct 10;353(1):37–42. doi: 10.1016/0014-5793(94)01007-2. [DOI] [PubMed] [Google Scholar]
  17. Lim N. F., Dascal N., Labarca C., Davidson N., Lester H. A. A G protein-gated K channel is activated via beta 2-adrenergic receptors and G beta gamma subunits in Xenopus oocytes. J Gen Physiol. 1995 Mar;105(3):421–439. doi: 10.1085/jgp.105.3.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Mager S., Min C., Henry D. J., Chavkin C., Hoffman B. J., Davidson N., Lester H. A. Conducting states of a mammalian serotonin transporter. Neuron. 1994 Apr;12(4):845–859. doi: 10.1016/0896-6273(94)90337-9. [DOI] [PubMed] [Google Scholar]
  20. Nargeot J., Lester H. A., Birdsall N. J., Stockton J., Wassermann N. H., Erlanger B. F. A photoisomerizable muscarinic antagonist. Studies of binding and of conductance relaxations in frog heart. J Gen Physiol. 1982 Apr;79(4):657–678. doi: 10.1085/jgp.79.4.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. North R. A., Williams J. T., Surprenant A., Christie M. J. Mu and delta receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5487–5491. doi: 10.1073/pnas.84.15.5487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Penington N. J., Kelly J. S., Fox A. P. Unitary properties of potassium channels activated by 5-HT in acutely isolated rat dorsal raphe neurones. J Physiol. 1993 Sep;469:407–426. doi: 10.1113/jphysiol.1993.sp019820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pfaffinger P. J., Martin J. M., Hunter D. D., Nathanson N. M., Hille B. GTP-binding proteins couple cardiac muscarinic receptors to a K channel. Nature. 1985 Oct 10;317(6037):536–538. doi: 10.1038/317536a0. [DOI] [PubMed] [Google Scholar]
  24. Reuveny E., Slesinger P. A., Inglese J., Morales J. M., Iñiguez-Lluhi J. A., Lefkowitz R. J., Bourne H. R., Jan Y. N., Jan L. Y. Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits. Nature. 1994 Jul 14;370(6485):143–146. doi: 10.1038/370143a0. [DOI] [PubMed] [Google Scholar]
  25. Tang W. J., Gilman A. G. Adenylyl cyclases. Cell. 1992 Sep 18;70(6):869–872. doi: 10.1016/0092-8674(92)90236-6. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wickman K. D., Iñiguez-Lluhl J. A., Davenport P. A., Taussig R., Krapivinsky G. B., Linder M. E., Gilman A. G., Clapham D. E. Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature. 1994 Mar 17;368(6468):255–257. doi: 10.1038/368255a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES