Chapter 7 : Inward Rectifier K Channels

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Inward Rectifier K Channels, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816452/9781555813284_Chap07-1.gif /docserver/preview/fulltext/10.1128/9781555816452/9781555813284_Chap07-2.gif


Inward rectifier K channels (Kirs) act as a valve or a diode, allowing an inward current upon hyperpolarization but not allowing exit of K ions upon depolarization. The degree of rectification in the Kir channels is correlated with the binding affinity of the channel for blocking cations. Kir channels thus serve diverse and important roles throughout the human body and pose major challenges in the recognition of the molecular basis of Kir-mediated channelopathies. The genes for this family of potassium channels encode proteins ranging from ~360 to 500 amino acids. A comprehensive sequence analysis of K channels in (CE), (DM), and mammalian genomes has been performed. Although the fundamental pore structure is the same in all members of the K channel family, other parts of the sequence indicate significant structural diversity. Phylogenetic analysis of the Kir genes grouped CE together, excluding the genes from the other two species, indicating that gene duplication occurred after the divergence of CE from the lineage-leading mammals and DM. Plants possess K channels that conduct primarily at negative voltages. The inward rectification of these K channels in plants is independent of intracellular magnesium, thus differing mechanistically from gating of Kir channels in the animal kingdom. Moreover, chimeras of plant and animal Kirs that contain the S1 to S4 segments of plants are activated by hyperpolarization, suggesting that plant Kirs have a membrane topology similar to that of eukaryotic Kv channels.

Citation: Shrivastava I, Guy H. 2005. Inward Rectifier K Channels, p 123-132. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch7
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Classification and nomenclature of major human Kir channels are shown. Also indicated are the alternative names in parentheses.

Citation: Shrivastava I, Guy H. 2005. Inward Rectifier K Channels, p 123-132. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Cartoon representation of multimeric association of Kir subunits. (left) Homomeric association of tetramers; (middle) heteromeric association; (right) coassembly of Kir subunits with SURs.

Citation: Shrivastava I, Guy H. 2005. Inward Rectifier K Channels, p 123-132. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

General topology of TM domain of Kirs. The dotted lines indicate approximate positions of the bilayer interfaces. (left) The TM helices are denoted as M1-P-M2; (right) association of Kir with intracellular SUR.

Citation: Shrivastava I, Guy H. 2005. Inward Rectifier K Channels, p 123-132. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch7
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abraham, M. R.,, A. Jahangir,, A. E. Alekseev,, and A. Terzic. 1999. Channelopathies of inwardly rectifying potassium channels. FASEB. J. 13: 1901 1910.
2. Ashcroft, F. M.,, and F. M. Gribble. 1998. Correlating structure and function in ATP sensitive K +channels. Trends Neurosci. 21: 288 294.
3. Bichet, D.,, F. A. Haas,, and L. Y. Jan. 2003. Merging functional studies with structures of inward rectifier K + channels. Nat. Rev. Neurosci. 4: 957 967.
4. Bond, C. T, M. Pessia, X. M. Xia, A. Lagrutta, M. P. Kavanaugh, and J. P. Adelman. 1994. Cloning and expression of a family of inward rectifier potassium channels. Recept. Channels 2: 183 191.
5. Cao, Y.,, N. M. Crawford,, and J. I. Schroeder. 1995 Amino terminus and the first four membrane spanning segments of the Arabidopsis K +channel KAT1 confer inward-rectification property of plant-animal chimeric channels. J. Biol. Chem. 270: 17697 17701.
6. Chan, K. W.,, J. L. Sui,, M. Vivadou,, and D. E. Logothetis. 1996. Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K +channel subunit. Proc. Natl. Acad. Sci. USA 93: 14193 14198.
7. Chen, G. Q.,, C. Cui,, M. L. Mayer,, and E. Gouaux. 1999. Functional characterization of a potassium-selective prokaryotic glutamate receptor. Nature 402: 817 821.
8. Clement, J. P.,, K. Kunjilwar,, G. Gonzalez,, M. Schwanstecher,, U. Panten,, B. L. Aguilar,, and J. Bryan. 1997. Association and stoichiometry of K(ATP) channel subunits. Neuron 18: 827 838.
9. Coetzee, W. A.,, Y. Amarillo,, J. Chiu,, A. Chow,, T. McCormack,, H. Moreno,, M. Nadal,, A. Ozaita,, D. Pountney,, E. Vega-SaenzdeMiera,, and B. Rudy,. 1999. Molecular diversity of K +channels. In B. Rudy, and P. Seeburg (ed.), Molecular and Functional Diversity of Ion Channels and Receptors. New York Academy of Sciences, New York, N.Y.
10. Corey, S.,, and D. E. Clapham. 1998. Identification of native atrial G-protein-regulated inwardly rectifying K + (GIRK4) channel homomultimers. J. Biol. Chem. 273: 27499 27504.
11. Dascal, N.,, W. Schreibmayer,, N. F. Lim,, W. Wang,, C. Chavkin,, L. DiMagno,, C. Labarca,, B. L. Kieffer,, C. Gaveriaux-Ruff,, D. Trollinger,, H. A. Lester,, and N. Davidson. 1993. Atrial G protein-activated K +channel: expression cloning and molecular properties. Proc. Natl. Acad. Sci. USA 90: 10235 10239.
12. Doring, F.,, C. Derst,, E. Wischmeyer,, C. Karschin,, R. Schneggenburger,, J. Daut,, and A. Karschin. 1998. The epithelial inward rectifier channel Kir7.1 displays unusual K +permeation properties. J. Neurosci. 18: 8625 8636.
13. Doupnik, C. A.,, and N. L. Davidson. 1995. The inward rectifier potassium channel family. Curr. Opin. Neurobiol. 5: 268 277.
14. Doyle, D. A.,, J. M. Cabral,, R. A. Pfuetzner,, A. Kuo,, J. M. Gulbis,, S. L. Cohen,, B. T. Chait,, and R. MacKinnon. 1998. The structure of potassium channel: molecular basis of K +conduction and selectivity. Science 280: 69 76.
15. Durell, S. R.,, and H. R. Guy. 2001a. A family of putative Kir potassium channels in prokaryotes. BMC Evol. Biol. 1: 14.
16. Durell, S. R.,, and H. R. Guy. 2001b. A putative prokaryote voltage-gated Ca 2+channel with only one 6TM motif per subunit. Biochem. Biophys. Res. Commun. 281: 741 746.
17. Fakler, B.,, U. Brandle,, E. Glowatzki,, H. P. Zenner,, and J. P. Ruppersberg. 1994. Kir2.1 inward rectifier K + channels are regulated independently by protein kinases and ATP hydrolysis. Neuron 13: 1413 1420.
18. George, A. L. 1995. Molecular genetics of ion channel diseases. Kidney Int. 48: 1180 1190.
19. Heginbotham, L.,, Z. Lu,, T. Abramson,, and R. MacKinnon. 1994. Mutations in the K +channel signature sequence. Biophys. J. 66: 1061 1067.
20. Higgins, C. 1995. The ABC of channel regulation. Cell 82: 693 696.
21. Hille, B. 2001. Ion Channels of Excitable Membranes, 3rd ed., Sinauer, Sunderland, Mass.
22. Ho, K.,, C. G. Nichols,, W. J. Lederer,, J. Lytton,, P. M. Vassilev,, M. V. Kanazirska,, and S. C. Hebert. 1993. Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature 362: 31 38.
23. Imredy, J. P.,, C. Chen,, and R. MacKinnon. 1998. A snake toxin inhibitor of inward rectifier potassium channel ROMK1. Biochemistry 37: 14867 14874.
24. Inagaki, N.,, Y. Tsuura,, N. Namba,, K. Masuda,, H. T. Gonoi,, M. Horie,, Y. Seino,, M. Mizuta,, and S. Seino. 1995. Cloning and functional characterization of a novel ATP sensitive potassium channel, ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle and heart. J. Biol. Chem. 270: 5691 5694.
25. Jiang, C.,, Z. Qu,, and H. Xu. 2002. Gating of inward rectifier K +channels by proton-mediated interactions of intracellular protein domains. Trends Cardiovasc. Med. 12: 5 13.
26. Jin, W.,, and Z. Lu. 1998. A novel high-affinity inhibitor for inward rectifier K +channels. Biochemistry 37: 13291 13299.
27. Keating, M. T.,, and M. C. Sanguinetti. 1996. Pathophysiology of ion channel mutations. Curr. Opin. Genet. Dev. 6: 326 333.
28. Krapivinsky, G.,, E. A. Gordon,, K. Wickman,, B. Velimirovic,, L. Krapivinsky,, and D. E. Clapham. 1995. The G-protein-gated atrial K +channel IKACh is a heteromultimer of two inwardly rectifying K +channel proteins. Nature 374: 135 141.
29. Krapivinsky, G.,, I. Medina,, L. Eng,, L. Krapivinsky,, Y. Yang,, and D. E. Clapham. 1998. A novel inward rectifier K +channel with unique pore properties. Neuron 20: 995 1005.
30. Kubo, Y.,, T. J. Baldwin,, Y. N. Jan,, and L. Y. Jan. 1993. Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 362: 127 133.
31. Kuo, A.,, J. M. Gulbis,, J. F. Antcliff,, T. Rahman,, E. D. Lowe,, J. Zimmer,, J. Cuthbertson,, F. M. Ashcroft,, T. Ezaki,, and D. A. Doyle. 2003. Crystal structure of the potassium channel KirBac1.1 in the closed state. Science 300: 1922 1926.
32. Lesage, F.,, F. Duprat,, M. Fink,, E. Guillemare,, T. Coppola,, M. Lazdunski,, and J.-P. Hugnot. 1994. Cloning provides evidence for a family of inward rectifier and G-protein coupled K +channels in the brain. FEBS Lett. 353: 37 42.
33. Liu, Y.,, E. McKenna,, D. J. Figueroa,, R. Blevins,, C. P. Austin,, P. B. Bennett,, and R. Swanson. 2000. The human inward rectifier K +channel subunit. Kir5.1 (KCNJ16) maps to chromosome 17q25 and is expressed in kidney and pancreas. Cytogenet. Cell Genet. 90: 60 63.
34. Lopatin, A. N.,, E. N. Makhina,, and C. G. Nichols. 1994. Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification. Nature 372: 366 369.
35. Lu, Z.,, and R. MacKinnon. 1997. Purification, characterization, and synthesis of an inward-rectifier K +channel inhibitor from scorpion venom. Biochemistry 36: 6936 6940.
36. Mao, J.,, J. Wu,, F. Chen,, X. Wang,, and C. Jiang. 2003. Inhibition of G-protein coupled inward rectifying K + channels by intracellular acidosis. J. Biol. Chem. 278: 7091 7098.
37. Matsuda, H.,, A. Saigusa,, and H. Irisawa. 1987. Ohmic conductance through the inwardly rectifying K +channel and blocking by internal Mg 2+. Nature 325: 156 159.
38. Minor, D. L.,, S. J. Masseling,, Y. N. Jan,, and L. Y. Jan. 1999. Transmembrane structure of an inwardly rectifying potassium channel. Cell 96: 879 891.
39. Moulton, G.,, T. K. Attwood,, D. J. Parry-Smith,, and J. C. L. Packer. 2003. Phylogenomic analysis and evolution of the potassium gene family. Recept. Channels 9: 363 377.
40. Navarro, B.,, S. A. Corey,, M. Kennedy,, and D. E. Clapham. 1996. Nonselective and G-βγ-insensitive weaver K +channels. Science 272: 1950 1953.
41. Nichols, C. G.,, and A. N. Lopatin. 1997. Inward rectifier potassium channels. Annu. Rev. Physiol. 69: 171 191.
42. Nichols, C. G.,, S.-L. Shyng,, A. Nestorowicz,, A. Glaser,, J. P. Clement IV,, G. Gonzalez,, A. Aguilar-Bryan,, M. A. Permutt,, and J. B. Stable. 1996. ADP as the intracellular regulator of insulin secretion. Science 272: 1785 1787.
43. Nishida, M.,, and R. MacKinnon. 2002. Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier at 1.8 Å resolution. Cell 111: 957 965.
44. North, R. A. 1989. Drug receptors and the inhibition of nerve cells. Br. J. Pharmacol. 98: 13 28.
45. Patil, N.,, D. R. Cox,, D. Bhat,, M. Faham,, R. M. Meyers,, and A. S. Peterson. 1995. A potassium channel mutation in weaver mice implicates membrane excitablility in granule cell differentiation. Nat. Genet. 11: 126 129.
46. Pessia, M.,, C. T. Bond,, M. P. Kavanaugh,, and J. P. Adelman. 1995. Contributions of the C-terminal domain to gating properties of inward rectifier potassium channels. Neuron 14: 1039 1045.
47. Pessia, M.,, S. J. Tucker,, K. Lee,, C. T. Bond,, and J. P. Adelman. 1996. Subunit positional effects revealed by novel heteromeric inwardly rectifying K +channels. EMBO J. 15: 2980 2987.
48. Reimann, F.,, and F. M. Ashcroft. 1999. Inwardly rectifying potassium channels. Curr. Opin. Cell. Biol. 11: 503 508.
49. Shieh, R. C.,, J. C. Chang,, and C. C. Kuo. 1999. K +binding sites and interactions between permeating K +ions at the external pore mouth of an inward rectifier K +;channel (Kir2.1). J. Biol. Chem. 274: 17424 17430.
50. Silverman, S. K.,, H. A. Lester,, and D. A. Dougherty. 1998. Asymmetrical contributions of subunit pore regions to ion selectivity in an inward rectifier K +channel. Biophys. J. 75: 1330 1339.
51. Taglialatela, M.,, B. A. Wible,, R. Caporaso,, and A. M. Brown. 1994. Specification of pore properties by the carboxyl terminus of inwardly rectifying K +channels. Science 264: 844 847.
52. Takumi, T.,, T. Ishii,, Y. Horio,, K.-I. Morishige,, N. Takahashi,, M. Yamada,, T. Yamashita,, H. Kiyama,, K. Sohmiya,, S. Nakanishi,, and Y. Kurachi. 1995. A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells . J. Biol. Chem. 270: 16339 16346.
53. Vandenberg, C. A. 1987. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc. Natl. Acad. Sci. USA 84: 2560 2564.
54. Wible, B. A.,, M. De Biasi,, K. Majumder,, M. Taglialatela,, and A. M. Brown. 1995. Cloning and functional expression of an inwardly rectifying K +channel from human atrium. Circ. Res. 76: 343 350.
55. Yamada, M.,, A. Ianobe,, and Y. Kurachi. 1998. G protein regulation of potassium channels. Pharmacol. Rev. 50: 723 757.
56. Yang, J.,, M. Yu,, Y. N. Jan,, and L. Y. Jan. 1997. Stabilization of ion selectivity filter by pore loop ion pairs in inwardly rectifying potassium channel. Proc. Natl. Acad. Sci. USA 94: 1568 1572.
57. Yano, H.,, L. H. Philipson,, J. L. Kugler,, Y. Tokuyama,, E. M. Davis,, M. M. Le Beau,, D. J. Nelson,, G. I. Bell,, and J. Takeda. 1994. Alternative splicing of human inwardly rectifying K +channel ROMK1 mRNA. Mol. Pharmacol. 45: 854 860.
58. Zhou, H.,, S. S. Tate,, and L. G. Plamer. 1994. Primary structure and functional properties of an epithelial K channel. Am. J. Physiol. 266: C809 C824.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error