BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Ca2+-regulated ion channels

  • Cox, Daniel H. (Department of Neuroscience, Tufts University School of Medicine)
  • Received : 2011.09.20
  • Published : 2011.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Due to its high external and low internal concentration the $Ca^{2+}$ ion is used ubiquitously as an intracellular signaling molecule, and a great many $Ca^{2+}$-sensing proteins have evolved to receive and propagate $Ca^{2+}$ signals. Among them are ion channel proteins, whose $Ca^{2+}$ sensitivity allows internal $Ca^{2+}$ to influence the electrical activity of cell membranes and to feedback-inhibit further $Ca^{2+}$ entry into the cytoplasm. In this review I will describe what is understood about the $Ca^{2+}$ sensing mechanisms of the three best studied classes of $Ca^{2+}$-sensitive ion channels: Large-conductance $Ca^{2+}$-activated $K^+$ channels, small-conductance $Ca^{2+}$-activated $K^+$ channels, and voltage-gated $Ca^{2+}$ channels. Great strides in mechanistic understanding have be made for each of these channel types in just the past few years.

Keywords

References

  1. Clapham, D. E. (2007) Calcium signaling. Cell 131, 1047-1058. https://doi.org/10.1016/j.cell.2007.11.028
  2. Williams, R. J. P. (1999) Calcium as a Cellular Regulator. Oxford University press, Oxford.
  3. Celio, M. R., Pauls, T. L. and Schwaller, B. (1996) Guidebook to the Calcium-binding Proteins. Oxford University Press, Oxford.
  4. Kunzelmann, K., Kongsuphol, P., Chootip, K., Toledo, C., Martins, J. R., Almaça, J., Tian, Y., Witzgall, R., Ousingsawat, J. and Schreiber, R. (2011) Role of the $Ca^{2+}$activated Cl- channels bestrophin and anoctamin in epithelial cells. Biol. Chem. 392, 125-134. https://doi.org/10.1515/BC.2011.010
  5. Ferrera, L., Caputo, A. and Galietta, L. J. V. (2010) TMEM 16A protein: a new identity for $Ca^{2+}$-dependent $Cl^-$ channels. Physiology (Bethesda, Md.) 25, 357-363. https://doi.org/10.1152/physiol.00030.2010
  6. Ramsey, I. S., Delling, M. and Clapham, D. E. (2006) An introduction to TRP channels. Annu. Rev. Physiol. 68, 619-647. https://doi.org/10.1146/annurev.physiol.68.040204.100431
  7. Lee, U. S. and Cui, J. (2010) BK channel activation: structural and functional insights. Trends Neurosci. 33, 415-423. https://doi.org/10.1016/j.tins.2010.06.004
  8. Butler, A., Tsunoda, S., McCobb, D. P., Wei, A. and Salkoff, L. (1993) mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels. Science 261, 221-224. https://doi.org/10.1126/science.7687074
  9. Brenner, R., Jegla, T. J., Wickenden, A., Liu, Y. and Aldrich, R. W. (2000) Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J. Biol. Chem. 275, 6453-6461. https://doi.org/10.1074/jbc.275.9.6453
  10. McManus, O. B., Helms, L. M., Pallanck, L., Ganetzky, B., Swanson, R. and Leonard, R. J. (1995) Functional role of the beta subunit of high conductance calcium-activated potassium channels. Neuron 14, 645-650. https://doi.org/10.1016/0896-6273(95)90321-6
  11. Lu, R., Alioua, A., Kumar, Y., Eghbali, M., Stefani, E. and Toro, L. (2006) MaxiK channel partners: physiological impact. J. Physiol. 570, 65-72. https://doi.org/10.1113/jphysiol.2005.098913
  12. Adelman, J. P., Shen, K. Z., Kavanaugh, M. P., Warren, R. A., Wu, Y. N., Lagrutta, A., Bond, C. T. and North, R. A. (1992) Calcium-activated potassium channels expressed from cloned complementary DNAs. Neuron 9, 209-216. https://doi.org/10.1016/0896-6273(92)90160-F
  13. Atkinson, N. S., Robertson, G. A. and Ganetzky, B. (1991) A component of calcium-activated potassium channels encoded by the Drosophila slo locus. Science 253, 551-555. https://doi.org/10.1126/science.1857984
  14. Meera, P., Wallner, M., Song, M. and Toro, L. (1997) Large conductance voltage- and calcium-dependent $K^+$ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc. Natl. Acad. Sci. U. S. A. 94, 14066-14071. https://doi.org/10.1073/pnas.94.25.14066
  15. Barrett, J. N., Magleby, K. L. and Pallotta, B. S. (1982) Properties of single calcium-activated potassium channels in cultured rat muscle. J. Physiol. (Lond) 331, 211-230. https://doi.org/10.1113/jphysiol.1982.sp014370
  16. Cui, J., Cox, D. H. and Aldrich, R. W. (1997) Intrinsic voltage dependence and $Ca^{2+}$ regulation of mslo large conductance Ca-activated $K^+$ channels. J. Gen. Physiol. 109, 647-673. https://doi.org/10.1085/jgp.109.5.647
  17. Shi, J. and Cui, J. (2001) Intracellular $Mg^{2+}$ enhances the function of BK-type $Ca^{2+}$-activated $K^+$ channels. J. Gen. Physiol. 118, 589-606. https://doi.org/10.1085/jgp.118.5.589
  18. Shi, J., Krishnamoorthy, G., Yang, Y., Hu, L., Chaturvedi, N., Harilal, D., Qin, J. and Cui, J. (2002) Mechanism of magnesium activation of calcium-activated potassium channels. Nature 418, 876-880. https://doi.org/10.1038/nature00941
  19. Xia, X. M., Zeng, X. and Lingle, C. J. (2002) Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature 418, 880-884. https://doi.org/10.1038/nature00956
  20. Schreiber, M. and Salkoff, L. (1997) A novel calcium-sensing domain in the BK channel. Biophys. J. 73, 1355-1363. https://doi.org/10.1016/S0006-3495(97)78168-2
  21. Bao, L., Rapin, A. M., Holmstrand, E. C. and Cox, D. H. (2002) Elimination of the BK(Ca) channel's high-affinity $Ca^{2+}$ sensitivity. J. Gen. Physiol. 120, 173-189. https://doi.org/10.1085/jgp.20028627
  22. Zhang, G., Huang, S.-Y., Yang, J., Shi, J., Yang, X., Moller, A., Zou, X. and Cui, J. (2010) Ion sensing in the RCK1 domain of BK channels. Proc. Natl. Acad. Sci. U. S. A. 107, 18700-18705. https://doi.org/10.1073/pnas.1010124107
  23. Bao, L., Kaldany, C., Holmstrand, E. C. and Cox, D. H. (2004) Mapping the BKCa channel's "$Ca^{2+}$ bowl": sidechains essential for $Ca^{2+}$ sensing. J. Gen. Physiol. 123, 475-489. https://doi.org/10.1085/jgp.200409052
  24. Bian, S., Favre, I. and Moczydlowski, E. (2001) $Ca^{2+}$-binding activity of a COOH-terminal fragment of the Drosophila BK channel involved in $Ca^{2+}$-dependent activation. Proc. Natl. Acad. Sci. U. S. A. 98, 4776-4781. https://doi.org/10.1073/pnas.081072398
  25. Wang, L. and Sigworth, F. J. (2009) Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy. Nature 461, 292-295. https://doi.org/10.1038/nature08291
  26. Wu, Y., Yang, Y., Ye, S. and Jiang, Y. (2010) Structure of the gating ring from the human large-conductance $Ca^{2+}$-gated $K^{+}$ channel. Nature 466, 393-397. https://doi.org/10.1038/nature09252
  27. Yuan, P., Leonetti, M. D., Pico, A. R., Hsiung, Y. and MacKinnon, R. (2010) Structure of the human BK channel $Ca^{2+}$-activation apparatus at 3.0 A resolution. Science (New York, NY) 329, 182-186. https://doi.org/10.1126/science.1190414
  28. Jiang, Y., Lee, A., Chen, J., Cadene, M., Chait, B. T. and MacKinnon, R. (2002) Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417, 515-522. https://doi.org/10.1038/417515a
  29. Kim, H.-J., Lim, H.-H., Rho, S.-H., Eom, S. H. and Park, C.-S. (2006) Hydrophobic interface between two regulators of $K^+$ conductance domains critical for calcium-dependent activation of large conductance $Ca^{2+}$-activated $K^+$ channels. J. Biol. Chem. 281, 38573-38581. https://doi.org/10.1074/jbc.M604769200
  30. Ye, S., Li, Y., Chen, L. and Jiang, Y. (2006) Crystal structures of a ligand-free MthK gating ring: insights into the ligand gating mechanism of $K^+$ channels. Cell 126, 1161-1173. https://doi.org/10.1016/j.cell.2006.08.029
  31. Pau, V. P. T., Abarca-Heidemann, K. and Rothberg, B. S. (2010) Allosteric mechanism of $Ca^{2+}$ activation and $H^+$-inhibited gating of the MthK $K^+$ channel. J. Gen. Physiol. 135, 509-526. https://doi.org/10.1085/jgp.200910387
  32. Zadek, B. and Nimigean, C. M. (2006) Calcium-dependent gating of MthK, a prokaryotic potassium channel. J. Gen. Physiol. 127, 673-685. https://doi.org/10.1085/jgp.200609534
  33. Cox, D. H. (2006) BKCa-channel structure and function; in Biological Membrane Ion Channels, pp. 171-219, Springer Science+Business Media LLC.
  34. Sweet, T.-B. and Cox, D. H. (2008) Measurements of the BKCa channel's high-affinity $Ca^{2+}$ binding constants: effects of membrane voltage. J. Gen. Physiol. 132, 491-505. https://doi.org/10.1085/jgp.200810094
  35. Zhang, X., Solaro, C. R. and Lingle, C. J. (2001) Allosteric regulation of BK channel gating by $Ca^{2+}$ and $Mg^{2+}$ through a nonselective, low affinity divalent cation site. J. Gen. Physiol. 118, 607-636. https://doi.org/10.1085/jgp.118.5.607
  36. Kohler, M., Hirschberg, B., Bond, C. T., Kinzie, J. M., Marrion, N. V., Maylie, J. and Adelman, J. P. (1996) Smallconductance, calcium-activated potassium channels from mammalian brain. Science (New York, NY) 273, 1709-1714. https://doi.org/10.1126/science.273.5282.1709
  37. Aggarwal, S. K. and MacKinnon, R. (1996) Contribution of the S4 segment to gating charge in the Shaker $K^+$channel. Neuron 16, 1169-1177. https://doi.org/10.1016/S0896-6273(00)80143-9
  38. Sigg, D. and Bezanilla, F. (1997) Total charge movement per channel. The relation between gating charge displacement and the voltage sensitivity of activation. J. Gen. Physiol. 109, 27-39. https://doi.org/10.1085/jgp.109.1.27
  39. Ishii, T. M., Silvia, C., Hirschberg, B., Bond, C. T., Adelman, J. P. and Maylie, J. (1997) A human intermediate conductance calcium-activated potassium channel. Proc. Natl. Acad. Sci. U.S.A. 94, 11651-11656. https://doi.org/10.1073/pnas.94.21.11651
  40. Xia, X. M., Fakler, B., Rivard, A., Wayman, G., Johnson- Pais, T., Keen, J. E., Ishii, T., Hirschberg, B., Bond, C. T., Lutsenko, S., Maylie, J. and Adelman, J. P. (1998) Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature 395, 503-507. https://doi.org/10.1038/26758
  41. Yap, K. L., Kim, J., Truong, K., Sherman, M., Yuan, T. and Ikura, M. (2000) Calmodulin target database. J. Struct. Funct. Genomics 1, 8-14. https://doi.org/10.1023/A:1011320027914
  42. Yap, K. L., Ames, J. B., Swindells, M. B. and Ikura, M. (1999) Diversity of conformational states and changes within the EF-hand protein superfamily. Proteins 37, 499-507. https://doi.org/10.1002/(SICI)1097-0134(19991115)37:3<499::AID-PROT17>3.0.CO;2-Y
  43. Bahler, M. and Rhoads, A. (2002) Calmodulin signaling via the IQ motif. FEBS Lett. 513, 107-113. https://doi.org/10.1016/S0014-5793(01)03239-2
  44. Schumacher, M. A., Rivard, A. F., Bachinger, H. P. and Adelman, J. P. (2001) Structure of the gating domain of a $Ca^{2+}$-activated $K^+$ channel complexed with $Ca^{2+}$/calmodulin. Nature 410, 1120-1124. https://doi.org/10.1038/35074145
  45. Schumacher, M. A., Crum, M. and Miller, M. C. (2004) Crystal structures of apocalmodulin and an apocalmodulin/SK potassium channel gating domain complex. Structure (London, England : 1993) 12, 849-860. https://doi.org/10.1016/j.str.2004.03.017
  46. Linse, S., Helmersson, A. and Forsen, S. (1991) Calcium binding to calmodulin and its globular domains. J. Biol. Chem. 266, 8050-8054.
  47. Stefan, M. I., Edelstein, S. J. and Le Novère, N. (2008) An allosteric model of calmodulin explains differential activation of PP2B and CaMKII. Proc. Natl. Acad. Sci. U. S. A. 105, 10768-10773. https://doi.org/10.1073/pnas.0804672105
  48. Catterall, W. A. (2011) Voltage-gated calcium channels. Cold Spring Harbor Perspectives in Biology 3, 1-23.
  49. Chaudhuri, D., Issa, J. B. and Yue, D. T. (2007) Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels. J. Gen. Physiol. 129, 385-401. https://doi.org/10.1085/jgp.200709749
  50. DeMaria, C. D., Soong, T. W., Alseikhan, B. A., Alvania, R. S. and Yue, D. T. (2001) Calmodulin bifurcates the local $Ca^{2+}$ signal that modulates P/Q-type $Ca^{2+}$ channels. Nature 411, 484-489. https://doi.org/10.1038/35078091
  51. Dunlap, K. (2007) Calcium Channels Are Models of Self- Control. J. Gen. Physiol. 129, 379-383. https://doi.org/10.1085/jgp.200709786
  52. Imredy, J. P. and Yue, D. T. (1994) Mechanism of $Ca^{2+}$-sensitive inactivation of L-type $Ca^{2+}$ channels. Neuron 12, 1301-1318. https://doi.org/10.1016/0896-6273(94)90446-4
  53. Lee, A., Scheuer, T. and Catterall, W. A. (2000) $Ca^{2+}$/calmodulin- dependent facilitation and inactivation of P/Q-type $Ca^{2+}$ channels. J. Neurosci. 20, 6830-6838.
  54. Tadross, M. R., Dick, I. E. and Yue, D. T. (2008) Mechanism of local and global $Ca^{2+}$ sensing by calmodulin in complex with a $Ca^{2+}$ channel. Cell 133, 1228-1240. https://doi.org/10.1016/j.cell.2008.05.025
  55. Alseikhan, B. A., DeMaria, C. D., Colecraft, H. M. and Yue, D. T. (2002) Engineered calmodulins reveal the unexpected eminence of $Ca^{2+}$ channel inactivation in controlling heart excitation. Proc. Natl. Acad. Sci. U. S. A. 99, 17185-17190. https://doi.org/10.1073/pnas.262372999
  56. Catterall, W. A. and Few, A. P. (2008) Calcium channel regulation and presynaptic plasticity. Neuron 59, 882-901. https://doi.org/10.1016/j.neuron.2008.09.005
  57. Chaudhuri, D., Alseikhan, B. A., Chang, S. Y., Soong, T. W. and Yue, D. T. (2005) Developmental activation of calmodulin-dependent facilitation of cerebellar P-type $Ca^{2+}$ current. J. Neurosci. 25, 8282-8294. https://doi.org/10.1523/JNEUROSCI.2253-05.2005
  58. Lacinova, L. (2005) Voltage-dependent calcium channels. Gen. Physiol. Biophys. 24 (Suppl 1), 1-78. https://doi.org/10.1152/physiolgenomics.00278.2005
  59. Ertel, E. A., Campbell, K. P., Harpold, M. M., Hofmann, F., Mori, Y., Perez-Reyes, E., Schwartz, A., Snutch, T. P., Tanabe, T., Birnbaumer, L., Tsien, R. W. and Catterall, W. A. (2000) Nomenclature of voltage-gated calcium channels. Neuron 25, 533-535. https://doi.org/10.1016/S0896-6273(00)81057-0
  60. Brehm, P., Eckert, R. and Tillotson, D. (1980) Calciummediated inactivation of calcium current in Paramecium. J. Physiol. 306, 193-203. https://doi.org/10.1113/jphysiol.1980.sp013391
  61. Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W. and Yue, D. T. (2008) A modular switch for spatial $Ca^{2+}$ selectivity in the calmodulin regulation of CaV channels. Nature 451, 830-834. https://doi.org/10.1038/nature06529
  62. Lee, A., Wong, S. T., Gallagher, D., Li, B., Storm, D. R., Scheuer, T. and Catterall, W. A. (1999) $Ca^{2+}$/calmodulin binds to and modulates P/Q-type calcium channels. Nature 399, 155-159. https://doi.org/10.1038/20194
  63. Borst, J. G. and Sakmann, B. (1998) Facilitation of presynaptic calcium currents in the rat brainstem. J. Physiol. 513 (Pt 1), 149-155. https://doi.org/10.1111/j.1469-7793.1998.149by.x
  64. Cuttle, M. F., Tsujimoto, T., Forsythe, I. D. and Takahashi, T. (1998) Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem. J. Physiol. 512 (Pt 3), 723-729. https://doi.org/10.1111/j.1469-7793.1998.723bd.x
  65. Chaudhuri, D., Chang, S. Y., DeMaria, C. D., Alvania, R. S., Soong, T. W. and Yue, D. T. (2004) Alternative splicing as a molecular switch for $Ca^{2+}$/calmodulin-dependent facilitationof P/Q-type $Ca^{2+}$ channels. J. Neurosci. 24, 6334-6342. https://doi.org/10.1523/JNEUROSCI.1712-04.2004
  66. Zuhlke, R. D., Pitt, G. S., Tsien, R. W. and Reuter, H. (2000) $Ca^{2+}$-sensitive inactivation and facilitation of L-type $Ca^{2+}$ channels both depend on specific amino acid residues in a consensus calmodulin-binding motif in the(alpha)1C sub-unit. J. Biol. Chem. 275, 21121-21129. https://doi.org/10.1074/jbc.M002986200
  67. Liang, H., DeMaria, C. D., Erickson, M. G., Mori, M. X., Alseikhan, B. A. and Yue, D. T. (2003) Unified mechanisms of $Ca^{2+}$ regulation across the $Ca^{2+}$ channel family. Neuron 39, 951-960. https://doi.org/10.1016/S0896-6273(03)00560-9
  68. Erickson, M. G., Alseikhan, B. A., Peterson, B. Z. and Yue, D. T. (2001) Preassociation of calmodulin with voltage-gated $Ca^{2+}$ channels revealed by FRET in single living cells. Neuron 31, 973-985. https://doi.org/10.1016/S0896-6273(01)00438-X
  69. Mori, M. X., Erickson, M. G. and Yue, D. T. (2004) Functional stoichiometry and local enrichment of calmodulin interacting with $Ca^{2+}$ channels. Science (New York, NY) 304, 432-435. https://doi.org/10.1126/science.1093490
  70. Zuhlke, R. D., Pitt, G. S., Deisseroth, K., Tsien, R. W. and Reuter, H. (1999) Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature 399, 159-162. https://doi.org/10.1038/20200
  71. Lee, A., Zhou, H., Scheuer, T. and Catterall, W. A. (2003) Molecular determinants of $Ca^{2+}$/calmodulin-dependent regulation of Ca(v)2.1 channels. Proc. Natl. Acad. Sci. U. S. A. 100, 16059-16064. https://doi.org/10.1073/pnas.2237000100
  72. Minor, D. L. and Findeisen, F. (2010) Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation. Channels (Austin, Tex) 4, 459-474. https://doi.org/10.4161/chan.4.6.12867
  73. Peterson, B. Z., DeMaria, C. D., Adelman, J. P. and Yue, D. T. (1999) Calmodulin is the $Ca^{2+}$ sensor for $Ca^{2+}$-dependent inactivation of L-type calcium channels. Neuron 22, 549-558. https://doi.org/10.1016/S0896-6273(00)80709-6
  74. Fallon, J. L., Halling, D. B., Hamilton, S. L. and Quiocho, F. A. (2005) Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel. Structure (London, England : 1993) 13, 1881-1886. https://doi.org/10.1016/j.str.2005.09.021
  75. Kim, E. Y., Rumpf, C. H., Fujiwara, Y., Cooley, E. S., Van Petegem, F. and Minor, D. L. (2008) Structures of CaV2 $Ca^{2+}$/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation. Structure (London, England : 1993) 16, 1455-1467. https://doi.org/10.1016/j.str.2008.07.010
  76. Mori, M. X., Vander Kooi, C. W., Leahy, D. J. and Yue, D. T. (2008) Crystal structure of the CaV2 IQ domain in complex with $Ca^{2+}$/calmodulin: high-resolution mechanistic implications for channel regulation by $Ca^{2+}$. Structure (London, England : 1993) 16, 607-620. https://doi.org/10.1016/j.str.2008.01.011
  77. Van Petegem, F., Chatelain, F. C. and Minor, D. L. (2005) Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-$Ca^{2+}$/calmodulin complex. Nat. Struct. Mol. Biol. 12, 1108-1115. https://doi.org/10.1038/nsmb1027
  78. Cox, D. H. and Dunlap, K. (1994) Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence. J. Gen. Physiol. 104, 311-336. https://doi.org/10.1085/jgp.104.2.311
  79. Fakler, B. and Adelman, J. P. (2008) Control of K(Ca) channels by calcium nano/microdomains. Neuron 59, 873-881. https://doi.org/10.1016/j.neuron.2008.09.001
  80. Faber, E. S. L. (2009) Functions and modulation of neuronal SK channels. Cell Biochem. Biophys. 55, 127-139. https://doi.org/10.1007/s12013-009-9062-7
  81. Keen, J. E., Khawaled, R., Farrens, D. L., Neelands, T., Rivard, A., Bond, C. T., Janowsky, A., Fakler, B., Adelman, J. P. and Maylie, J. (1999) Domains responsible for constitutive and $Ca^{2+}$-dependent interactions between calmodulin and small conductance $Ca^{2+}$-activated potassium channels. J. Neurosci. 19, 8830-8838.

Cited by

  1. The inactivation domain of STIM1 is functionally coupled with the Orai1 pore to enable Ca2+-dependent inactivation vol.147, pp.2, 2016, https://doi.org/10.1085/jgp.201511438
  2. Calcium-activated potassium channel SK1 is widely expressed in the peripheral nervous system and sensory organs of adult zebrafish vol.555, 2013, https://doi.org/10.1016/j.neulet.2013.09.026