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Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels

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Voltage-Gated Calcium Channels

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

The passage of Ca2+ ions through voltage-gated Ca2+ channels triggers a wide range of signaling pathways but also fundamentally regulates further Ca2+ influx through these channels. Cav1.2 (L-type) and Cav2.1 (P/Q-type) channels undergo a dual feedback regulation by Ca2+, which is manifested as enhanced facilitation and inactivation of Ca2+ currents compared to Ba2+ currents. Ca2+-dependent facilitation and inactivation are distinct biophysical processes but are linked through a common molecular mechanism. The ubiquitous Ca2+-sensing protein calmodulin binds directly to multiple sequences in the Ca2+ channel α1 subunit, causing Ca2+-dependent conformational changes that favor facilitated or inactivated states of the channel. In the nervous system, Ca2+ binding proteins related to CaM also contribute to modulation of Ca2+ channels, which may diversify Ca2+ signaling in different neurons. In all excitable cells, Ca2+-dependent facilitation and inactivation of voltage-gated Ca2+ channels may be a general mechanism for fine-tuning Ca2+ entry to protect against toxic Ca2+ overloads and to control the specificity with which Ca2+-dependent signaling pathways are activated.

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References

  1. Naitoh Y. Ionic control of the reversal response of cilia in Paramecium caudatum. A calcium hypothesis. J Gen Physiol 1968; 51:85–103.

    Article  PubMed  CAS  Google Scholar 

  2. Brehm P, Eckert R. Calcium entry leads to inactivation of calcium channel in Paramecium. Science 1978; 202:1203–6.

    Article  PubMed  CAS  Google Scholar 

  3. Brehm P, Eckert R, Tillotson D. Calcium-mediated inactivation of calcium current in Paramecium. J Physiol 1980; 306:193–203.

    PubMed  CAS  Google Scholar 

  4. Tillotson D. Inactivation of Ca conductance dependent on entry of Ca ions in molluscan neurons. Proc Natl Acad Sci USA 1979; 76:1497–500.

    Article  PubMed  CAS  Google Scholar 

  5. Eckert R, Tillotson, DL. Calcium-mediated inactivation of the calcium conductance in caesium-loaded giant neurones of Aplysia californica. J Physiol 1981; 314:265–80.

    PubMed  CAS  Google Scholar 

  6. Eckert R, Chad JE. Inactivation of Ca channels. Prog Biophys Mol Biol 1984; 44:215–267.

    Article  PubMed  CAS  Google Scholar 

  7. Byerly L, Hagiwara S. Calcium channel diversity. In: Grinnell AD, Armstrong D, Jackson M, eds. Calcium and Ion Channel Modulation. New York: Plenum Press, Inc., 1990.

    Google Scholar 

  8. Kass RS, Sanguinetti MC. Inactivation of calcium channel current in the calf cardiac Purkinje fiber. Evidence for voltage-and calcium-mediated mechanisms. J Gen Physiol 1984; 84:705–26.

    Article  PubMed  CAS  Google Scholar 

  9. Mentrard D, Vassort G, Fischmeister R. Calcium-mediated inactivation of the calcium conductance in cesium-loaded frog heart cells. J Gen Physiol 1984; 83:105–31.

    Article  PubMed  CAS  Google Scholar 

  10. Lee KS, Marban E, Tsien RW. Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium. J Physiol 1985; 364:395–411.

    PubMed  CAS  Google Scholar 

  11. Hadley RW, Hume JR. An intrinsic potential-dependent inactivation mechanism associated with calcium channels in guinea-pig myocytes. J Physiol 1987; 389:205–22.

    PubMed  CAS  Google Scholar 

  12. Zühlke RG, Pitt GS, Deisseroth K et al. Calmodulin supports both inactivation and facilitation of L-type calcium channels. Nature 1999; 399:159–161.

    Article  PubMed  Google Scholar 

  13. Bechem M, Pott L. Removal of Ca current inactivation in dialysed guinea-pig atrial cardioballs by Ca chelators. Pflugers Arch 1985; 404:10–20.

    Article  PubMed  CAS  Google Scholar 

  14. Chad JE, Eckert R. An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones. J Physiol 1986; 378:31–51.

    PubMed  CAS  Google Scholar 

  15. Sherman A, Keizer J, Rinzel J. Domain model for Ca2+-inactivation of Ca2+ channels at low channel density. Biophys J 1990; 58:985–95.

    PubMed  CAS  Google Scholar 

  16. Imredy JP, Yue DT. Submicroscopic Ca2+ diffusion mediates inhibitory coupling between individual Ca2+ channels. Neuron 1992; 9:197–207.

    Article  PubMed  CAS  Google Scholar 

  17. Keizer J, Maki LW. Conditional probability analysis for a domain model of Ca2+-inactivation of Ca2+ channels. Biophys J 1992; 63:291–295.

    PubMed  CAS  Google Scholar 

  18. Yue DT, Backx PH, Imredy JP. Calcium-sensitive inactivation in the gating of single calcium channels. Science 1990; 250:1735–1738.

    Article  PubMed  CAS  Google Scholar 

  19. Imredy JP, Yue DT. Mechanism of Ca2+-sensitive inactivation of L-type Ca2+ channels. Neuron 1994; 12:1301–1318.

    Article  PubMed  CAS  Google Scholar 

  20. Xia XM, Fakler B, Rivard A et al. Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature 1998; 395:503–507.

    Article  PubMed  CAS  Google Scholar 

  21. Marban E, Tsien RW. Enhancement of calcium current during digitalis inotropy in mammalian heart: positive feed-back regulation by intracellular calcium? J Physiol 1982; 329:589–614.

    PubMed  CAS  Google Scholar 

  22. Mitra R, Morad M. Two types of calcium channels in guinea pig ventricular myocytes. Proc Natl Acad Sci 1986; 83:5340–4.

    Article  PubMed  CAS  Google Scholar 

  23. McCarron JG, McGeown JG, Reardon S et al. Calcium-dependent enhancement of calcium cur rent in smooth muscle by calmodulin-dependent protein kinase II. Nature 1992; 357:74–77.

    Article  PubMed  CAS  Google Scholar 

  24. Zygmunt AC, Maylie J. Stimulation-dependent facilitation of the high threshold calcium current in guinea-pig ventricular myocytes. J Physiol (Lond) 1990; 428:653–671

    PubMed  CAS  Google Scholar 

  25. Gurney AM, Charnet P, Pye JM et al. Augmentation of cardiac calcium current by flash photolysis of intracellular caged-Ca2+ molecules. Nature 1989; 341:65–68.

    Article  PubMed  CAS  Google Scholar 

  26. De Leon M, Wang Y, Jones L et al. Essential Ca2+-binding motif for Ca2+-sensitive inactivation of L-type Ca2+ channels. Science 1995; 270:1502–1506.

    Article  PubMed  Google Scholar 

  27. Adams B, Tanabe T. Structural regions of the cardiac Ca channel alpha subunit involved in Ca-dependent inactivation. J Gen Physiol 1997; 110:379–89.

    Article  PubMed  CAS  Google Scholar 

  28. Zhou JM, Olcese R, Qin N et al. Feedback inhibition of Ca2+ channels by Ca2+ depends on a short sequence of the C terminus that does not include the Ca2+-binding function of a motif with similarity to Ca2+-binding domains. Proc Natl Acad Sci USA 1997; 94:2301–2305.

    Article  PubMed  CAS  Google Scholar 

  29. Soldatov NM, Zühlke RD, Bouron A et al. Molecular structures involved in L-type calcium channel inactivation-Role of the carboxyl-terminal region encoded by exons 40–42 in α1C subunit in the kinetics and Ca2+ dependence of inactivation. J Biol Chem 1997; 272:3560–3566.

    Article  PubMed  CAS  Google Scholar 

  30. Soldatov NM, Oz M, O’Brien KA et al. Molecular determinants of L-type Ca2+ channel inactivation-Segment exchange analysis of the carboxyl-terminal cytoplasmic motif encoded by exons 40–42 of the human α1C subunit gene. J Biol Chem. 1998; 273:957–963.

    Article  PubMed  CAS  Google Scholar 

  31. Zühlke RD, Reuter H. Ca2+-sensitive inactivation of L-type Ca2+ channels depends on multiple cytoplasmic amino acid sequences of the α1C subunit. Proc Nad Acad Sci USA 1998; 95:3287–3294.

    Article  Google Scholar 

  32. Saimi Y, Kung C. Calmodulin as an ion channel subunit. Annu Rev Physiol 2002; 64:289–311.

    Article  PubMed  CAS  Google Scholar 

  33. Qin N, Olcese R, Bransby M et al. Ca2+-induced inhibition of the cardiac Ca2+ channel depends on calmodulin. Proc Natl Acad Sci 1999; 96:2435–2438.

    Article  PubMed  CAS  Google Scholar 

  34. Peterson BZ, DeMaria CD, Yue DT. Calmodulin is the Ca2+ sensor for Ca2+-dependent inactivation of 1-type calcium channels. Neuron 1999a;22:549–558.

    Article  PubMed  CAS  Google Scholar 

  35. James P, Vorherr T, Carafoli E. Calmodulin-binding domains: just two faced or multi-faceted? Trends Biochem Sci 1995; 20:38–42.

    Article  PubMed  CAS  Google Scholar 

  36. Pitt GS, Zuhlke RD, Hudmon A et al. Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channels. J Biol Chem 2001; 276:30794–802.

    Article  PubMed  CAS  Google Scholar 

  37. Erickson MG, Alseikhan BA, Peterson BZ et al. Preassociation of calmodulin with voltage-gated Ca2+ channels revealed by FRET in single living cells. Neuron 2001; 31:973–85.

    Article  PubMed  CAS  Google Scholar 

  38. Pate P, Mochca-Morales J, Wu Y et al. Determinants for calmodulin binding on voltage-dependent Ca2+ channels. J Biol Chem 2000; 275:39786–39792.

    Article  PubMed  CAS  Google Scholar 

  39. Romanin C, Gamsjaeger R, Kahr H et al. Ca2+ sensors of L-type Ca2+ channel. FEBS Lett 2000;487:301–6.

    Article  PubMed  CAS  Google Scholar 

  40. Ferreira G, Yi J, Rios E et al. Ion-dependent inactivation of barium current through L-type calcium channels. J Gen Physiol 1997; 109:449–461.

    Article  PubMed  CAS  Google Scholar 

  41. Patil PG, Brody DL, Yue DT. Preferential closed-state inactivation of neuronal calcium channels. Neuron 1998; 20:1027–1038.

    Article  PubMed  CAS  Google Scholar 

  42. Ivanina T, Blumenstein Y, Shistik E et al. Modulation of L-type Ca2+ channels by Gβγ and calmodulin via interactions with N and C termini of α1C J Biol Chem 2000; 275:39846–54.

    Article  PubMed  CAS  Google Scholar 

  43. Peterson BZ, Lee JS, Mulle JS et al. Individual amino acids within a consensus EF-hand motif are critical for calcium-dependent inactivation of α1C calcium channels. Biophys J 1999b; 76:A340.

    Google Scholar 

  44. Bernatchcz G, Talwar D, Parent L. Mutations in the EF-hand motif impair the inactivation of barium currents of the cardiac alpha1C channel. Biophys J 1998; 75:1727–39.

    Article  Google Scholar 

  45. Zuhlke RD, Pitt GS, Tsien RW et al. Ca2+-sensitive inactivation and facilitation of L-type Ca2+channels both depend on specific amino acid residues in a consensus calmodulin-binding motif in the α1C subunit. J Biol Chem 2000; 275:21121–9.

    Article  PubMed  CAS  Google Scholar 

  46. Schumacher MA, Rivard AF, Bachinger HP et al. Structure of the gating domain of a Ca2+-activated K+ channel complexed with Ca2+/calmodulin. Nature 2001; 410:1120–4.

    Article  PubMed  CAS  Google Scholar 

  47. Dzhura I, Wu Y, Colbran RJ et al. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol 2000; 2:173–7.

    Article  PubMed  CAS  Google Scholar 

  48. Wu Y, Colbran RJ, Anderson ME. Calmodulin kinase is a molecular switch for cardiac excitation-contraction coupling. Proc Natl Acad Sci USA 2001a; 98:2877–81.

    Article  PubMed  CAS  Google Scholar 

  49. Wu Y, Dzhura I, Colbran RJ et al. Calmodulin kinase and a calmodulin-binding ‘IQ’ domain facilitate L-type Ca2+ current in rabbit ventricular myocytes by a common mechanism. J Physiol 2001b; 535:679–87.

    Article  PubMed  CAS  Google Scholar 

  50. Tareilus E, Schoch J, Breer H. Ca2+-dependent inactivation of P-type calcium channels in nerve terminals. J Neurochem 1994; 62:2283–91.

    Article  PubMed  CAS  Google Scholar 

  51. Branchaw JL, Banks MI, Jackson MB. Ca2+-and voltage-dependent inactivation of Ca2+ channels in nerve terminals of the neurohypophysis. J Neurosci 1997; 17:5772–5781.

    PubMed  CAS  Google Scholar 

  52. Forsythe ID, Tsujimoto T, Barnes-Davies M et al. Inactivation of presynaptic calcium current contributes to synaptic depression at a fast central synapse. Neuron 1998; 20:797–807.

    Article  PubMed  CAS  Google Scholar 

  53. Borst JG, Sakmann B. Facilitation of presynaptic calcium currents in the rat brainstem. J Physiol 1998; 513:149–155.

    Article  PubMed  CAS  Google Scholar 

  54. Cuttle MF, Tsujimoto T, Forsythe ID et al. Facilitation of the presynaptic calcium current at an auditory synapse in rat brainstem. J Physiol 1998; 512:723–729.

    Article  PubMed  CAS  Google Scholar 

  55. Lee A, Wong ST, Gallagher D et al. Ca2+ /calmodulin binds to and modulates P/Q-type calcium channels. Nature 1999; 339:155–159.

    Google Scholar 

  56. Cens T, Mangoni ME, Nargeot J et al. Modulation of the α1A Ca2+ channel by β subunits at physiological Ca2+ concentration. FEBS Lett 1996; 391:232–237.

    Article  PubMed  CAS  Google Scholar 

  57. Lee A, Scheuer T, Catterall WA. Ca2+/ calmodulin-dependent facilitation and inactivation of P/Q-type Ca2+ channels. J Neurosci 2000; 20:6830–6838.

    PubMed  CAS  Google Scholar 

  58. DeMaria CD, Soong T, Alseikhan BA et al. Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels. Nature 2001; 411:484–489.

    Article  PubMed  CAS  Google Scholar 

  59. Bahler M, Rhoads A. Calmodulin signaling via the IQ motif. FEBS Lett 2002; 513:107–13.

    Article  PubMed  CAS  Google Scholar 

  60. Polans A, Baehr W, Palczewski K. Turned on by Ca2+! The physiology and pathology of Ca2+-binding proteins in the retina. Trends Neurosci 1996; 19:547–554.

    Article  PubMed  CAS  Google Scholar 

  61. Burgoyne RD, Weiss JL. The neuronal calcium sensor family of Ca2+-binding proteins. Biochem J 2001; 353:1–12.

    Article  PubMed  CAS  Google Scholar 

  62. Pongs O, Lindemeier J, Zhu XR et al. Frequenin-a novel calcium-binding protein that modulates synaptic efficacy in the Drosophila nervous system. Neuron 1993; 11:15–28.

    Article  PubMed  CAS  Google Scholar 

  63. McFerran BW, Graham ME, Burgoyne RD. Neuronal Ca2+ sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin and PC12 cells and regulates neurosecretion from dense-core granules. J Biol Chem 1998; 273:22768–22772.

    Article  PubMed  CAS  Google Scholar 

  64. Gomez M, De Castro E, Guarin E et al. Ca2+ signaling via the neuronal calcium sensor-1 regulates associative learning and memory in C. elegans. Neuron 2001; 30:241–248.

    Article  PubMed  CAS  Google Scholar 

  65. Wang C-Y, Yang F, He X et al. Ca2+-binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release. Neuron 2001; 32:99–112.

    Article  PubMed  Google Scholar 

  66. Weiss JL, Archer DA, Burgoyne RD. Neuronal Ca2+ sensor-1/frequenin functions in an autocrine pathway regulating Ca2+ channels in bovine adrenal chromaffin cells. J Biol Chem 2000;275:40082–40087.

    Article  PubMed  CAS  Google Scholar 

  67. Weiss JL, Burgoyne RD. Voltage-independent inhibition of P/Q-type calcium channels in adrenal chromaffin cells via a neuronal calcium sensor-1 dependent pathway involves src family tyrosine kinase. J Biol Chem 2001; 276:44804–44811.

    Article  PubMed  CAS  Google Scholar 

  68. Tsujimoto T, Jeromin A, Saitoh N et al. Neuronal calcium sensor 1 and activity-dependent facilitation of p/q-type calcium currents at presynaptic nerve terminals. Science 2002; 295:2276–9.

    Article  PubMed  CAS  Google Scholar 

  69. Haeseleer F, Sokal I, Verlinde CLMJ et al. Five members of a novel Ca2+-binding protein (CABP) subfamily with similarity to calmodulin. J Biol Chem 2000; 275:1247–1260.

    Article  PubMed  CAS  Google Scholar 

  70. Haeseleer F, Imanishi Y, Sokal I et al. Calcium-binding proteins: intracellular sensors from the calmodulin superfamily. Biochem Biophys Res Commun 2002; 290:615–23.

    Article  PubMed  CAS  Google Scholar 

  71. Lee A, Westenbroek RE, Haeseleer F et al. Differential modulation of Cav2.1 channels by calmodulin and Ca2+-binding protein 1. Nat Neuroscience 2002; 5:210–217.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Emory University, Altanta, Georgia, USA

    Amy Lee

  2. Department of Pharmacology, University of Washington, Seattle, Washington, USA

    William A. Catterall

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  1. Amy Lee
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  2. William A. Catterall
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Lee, A., Catterall, W.A. (2005). Ca2+-Dependent Modulation of Voltage-Gated Ca2+ Channels. In: Voltage-Gated Calcium Channels. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27526-6_11

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