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. 1996 Jun 17;15(12):2980–2987.

Subunit positional effects revealed by novel heteromeric inwardly rectifying K+ channels.

M Pessia 1, S J Tucker 1, K Lee 1, C T Bond 1, J P Adelman 1
PMCID: PMC450239  PMID: 8670799

Abstract

Kir 4.1 is an inward rectifier potassium channel subunit isolated from rat brain which forms homomeric channels when expressed in Xenopus oocytes; Kir 5.1 is a structurally related subunit which does not. Co-injection of mRNAs encoding Kir 4.1 and Kir 5.1 resulted in potassium currents that (i) were much larger than those seen from expression of Kir 4.1 alone, (ii) increased rather than decreased during several seconds at strongly negative potentials and (iii) had an underlying unitary conductance of 43 pS rather than the 12 pS seen with Kir 4.1 alone. In contrast, the properties of Kir 1.1, 2.1, 2.3, 3.1, 3.2 or 3.4 were not altered by coexpression with Kir 5.1. Expression of a concatenated cDNA encoding two or four linked subunits produced currents with the properties of co-expressed Kir 4.1 and Kir 5.1 when the subunits were connected 4-5 or 4-5-4-5, but not when they were connected 4-4-5-5. The results indicate that Kir 5.1 associates specifically with Kir 4.1 to form heteromeric channels, and suggest that they do so normally in the subunit order 4-5-4-5. Further, the relative order of subunits within the channel contributes to their functional properties.

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Selected References

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

  1. Barres B. A. Glial ion channels. Curr Opin Neurobiol. 1991 Oct;1(3):354–359. doi: 10.1016/0959-4388(91)90052-9. [DOI] [PubMed] [Google Scholar]
  2. Bond C. T., Ammälä C., Ashfield R., Blair T. A., Gribble F., Khan R. N., Lee K., Proks P., Rowe I. C., Sakura H. Cloning and functional expression of the cDNA encoding an inwardly-rectifying potassium channel expressed in pancreatic beta-cells and in the brain. FEBS Lett. 1995 Jun 19;367(1):61–66. doi: 10.1016/0014-5793(95)00497-w. [DOI] [PubMed] [Google Scholar]
  3. Bond C. T., Pessia M., Xia X. M., Lagrutta A., Kavanaugh M. P., Adelman J. P. Cloning and expression of a family of inward rectifier potassium channels. Receptors Channels. 1994;2(3):183–191. [PubMed] [Google Scholar]
  4. 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]
  5. Doupnik C. A., Davidson N., Lester H. A. The inward rectifier potassium channel family. Curr Opin Neurobiol. 1995 Jun;5(3):268–277. doi: 10.1016/0959-4388(95)80038-7. [DOI] [PubMed] [Google Scholar]
  6. Duprat F., Lesage F., Guillemare E., Fink M., Hugnot J. P., Bigay J., Lazdunski M., Romey G., Barhanin J. Heterologous multimeric assembly is essential for K+ channel activity of neuronal and cardiac G-protein-activated inward rectifiers. Biochem Biophys Res Commun. 1995 Jul 17;212(2):657–663. doi: 10.1006/bbrc.1995.2019. [DOI] [PubMed] [Google Scholar]
  7. Fakler B., Brändle U., Bond C., Glowatzki E., König C., Adelman J. P., Zenner H. P., Ruppersberg J. P. A structural determinant of differential sensitivity of cloned inward rectifier K+ channels to intracellular spermine. FEBS Lett. 1994 Dec 19;356(2-3):199–203. doi: 10.1016/0014-5793(94)01258-x. [DOI] [PubMed] [Google Scholar]
  8. Ferrer J., Nichols C. G., Makhina E. N., Salkoff L., Bernstein J., Gerhard D., Wasson J., Ramanadham S., Permutt A. Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels. J Biol Chem. 1995 Nov 3;270(44):26086–26091. doi: 10.1074/jbc.270.44.26086. [DOI] [PubMed] [Google Scholar]
  9. Glowatzki E., Fakler G., Brändle U., Rexhausen U., Zenner H. P., Ruppersberg J. P., Fakler B. Subunit-dependent assembly of inward-rectifier K+ channels. Proc Biol Sci. 1995 Aug 22;261(1361):251–261. doi: 10.1098/rspb.1995.0145. [DOI] [PubMed] [Google Scholar]
  10. Hagiwara S., Yoshii M. Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion. J Physiol. 1979 Jul;292:251–265. doi: 10.1113/jphysiol.1979.sp012849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ho K., Nichols C. G., Lederer W. J., Lytton J., Vassilev P. M., Kanazirska M. V., Hebert S. C. Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature. 1993 Mar 4;362(6415):31–38. doi: 10.1038/362031a0. [DOI] [PubMed] [Google Scholar]
  12. Horton R. M., Hunt H. D., Ho S. N., Pullen J. K., Pease L. R. Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene. 1989 Apr 15;77(1):61–68. doi: 10.1016/0378-1119(89)90359-4. [DOI] [PubMed] [Google Scholar]
  13. Hurst R. S., Kavanaugh M. P., Yakel J., Adelman J. P., North R. A. Cooperative interactions among subunits of a voltage-dependent potassium channel. Evidence from expression of concatenated cDNAs. J Biol Chem. 1992 Nov 25;267(33):23742–23745. [PubMed] [Google Scholar]
  14. Hurst R. S., North R. A., Adelman J. P. Potassium channel assembly from concatenated subunits: effects of proline substitutions in S4 segments. Receptors Channels. 1995;3(4):263–272. [PubMed] [Google Scholar]
  15. 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]
  16. Kubo Y., Baldwin T. J., Jan Y. N., Jan L. Y. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature. 1993 Mar 11;362(6416):127–133. doi: 10.1038/362127a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Leech C. A., Stanfield P. R. Inward rectification in frog skeletal muscle fibres and its dependence on membrane potential and external potassium. J Physiol. 1981;319:295–309. doi: 10.1113/jphysiol.1981.sp013909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Lewis D. L., Ikeda S. R., Aryee D., Joho R. H. Expression of an inwardly rectifying K+ channel from rat basophilic leukemia cell mRNA in Xenopus oocytes. FEBS Lett. 1991 Sep 23;290(1-2):17–21. doi: 10.1016/0014-5793(91)81215-t. [DOI] [PubMed] [Google Scholar]
  21. Lopatin A. N., Makhina E. N., Nichols C. G. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature. 1994 Nov 24;372(6504):366–369. doi: 10.1038/372366a0. [DOI] [PubMed] [Google Scholar]
  22. Lu Z., MacKinnon R. Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel. Nature. 1994 Sep 15;371(6494):243–246. doi: 10.1038/371243a0. [DOI] [PubMed] [Google Scholar]
  23. Matsuda H., Saigusa A., Irisawa H. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature. 1987 Jan 8;325(7000):156–159. doi: 10.1038/325156a0. [DOI] [PubMed] [Google Scholar]
  24. McKinney L. C., Gallin E. K. Inwardly rectifying whole-cell and single-channel K currents in the murine macrophage cell line J774.1. J Membr Biol. 1988 Jul;103(1):41–53. doi: 10.1007/BF01871931. [DOI] [PubMed] [Google Scholar]
  25. Mihara S., North R. A., Surprenant A. Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones. J Physiol. 1987 Sep;390:335–355. doi: 10.1113/jphysiol.1987.sp016704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morishige K., Takahashi N., Findlay I., Koyama H., Zanelli J. S., Peterson C., Jenkins N. A., Copeland N. G., Mori N., Kurachi Y. Molecular cloning, functional expression and localization of an inward rectifier potassium channel in the mouse brain. FEBS Lett. 1993 Dec 28;336(3):375–380. doi: 10.1016/0014-5793(93)80840-q. [DOI] [PubMed] [Google Scholar]
  27. Pessia M., Bond C. T., Kavanaugh M. P., Adelman J. P. Contributions of the C-terminal domain to gating properties of inward rectifier potassium channels. Neuron. 1995 May;14(5):1039–1045. doi: 10.1016/0896-6273(95)90342-9. [DOI] [PubMed] [Google Scholar]
  28. Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sakmann B., Trube G. Voltage-dependent inactivation of inward-rectifying single-channel currents in the guinea-pig heart cell membrane. J Physiol. 1984 Feb;347:659–683. doi: 10.1113/jphysiol.1984.sp015089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Silver M. R., DeCoursey T. E. Intrinsic gating of inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg2+. J Gen Physiol. 1990 Jul;96(1):109–133. doi: 10.1085/jgp.96.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Standen N. B., Stanfield P. R. A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions. J Physiol. 1978 Jul;280:169–191. doi: 10.1113/jphysiol.1978.sp012379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stanfield P. R., Davies N. W., Shelton P. A., Khan I. A., Brammar W. J., Standen N. B., Conley E. C. The intrinsic gating of inward rectifier K+ channels expressed from the murine IRK1 gene depends on voltage, K+ and Mg2+. J Physiol. 1994 Feb 15;475(1):1–7. doi: 10.1113/jphysiol.1994.sp020044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tucker S. J., Bond C. T., Herson P., Pessia M., Adelman J. P. Inhibitory interactions between two inward rectifier K+ channel subunits mediated by the transmembrane domains. J Biol Chem. 1996 Mar 8;271(10):5866–5870. doi: 10.1074/jbc.271.10.5866. [DOI] [PubMed] [Google Scholar]
  34. Tytgat J., Hess P. Evidence for cooperative interactions in potassium channel gating. Nature. 1992 Oct 1;359(6394):420–423. doi: 10.1038/359420a0. [DOI] [PubMed] [Google Scholar]
  35. Vandenberg C. A. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2560–2564. doi: 10.1073/pnas.84.8.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wible B. A., Taglialatela M., Ficker E., Brown A. M. Gating of inwardly rectifying K+ channels localized to a single negatively charged residue. Nature. 1994 Sep 15;371(6494):246–249. doi: 10.1038/371246a0. [DOI] [PubMed] [Google Scholar]
  37. Yang J., Jan Y. N., Jan L. Y. Determination of the subunit stoichiometry of an inwardly rectifying potassium channel. Neuron. 1995 Dec;15(6):1441–1447. doi: 10.1016/0896-6273(95)90021-7. [DOI] [PubMed] [Google Scholar]
  38. Yang X. C., Sachs F. Block of stretch-activated ion channels in Xenopus oocytes by gadolinium and calcium ions. Science. 1989 Feb 24;243(4894 Pt 1):1068–1071. doi: 10.1126/science.2466333. [DOI] [PubMed] [Google Scholar]

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