Skip to main content
Log in

Ca2+ channel Ca2+-dependent inactivation in a mammalian central neuron involves the cytoskeleton

  • Original Article
  • Neurophysiology, Muscle and Sensory Organs
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Ca2+ channel inactivation was investigated in acutely isolated hippocampal pyramidal neurons from adult rats and found to have a component dependent on intracellular Ca2+. Ca2+-dependent inactivation was identified as the additional inactivation of channel current observed when Ca2+ replaced Ba2+ as the current carrying ion, and was found to be an independent process from that of Ba2+ current inactivation based on three lines of evidence: (1) no correlation between Ca2+-dependent inactivation and Ba2+ current inactivation was found, (2) only Ca2+-dependent inactivation was reduced by intracellular application of Ca2+ chelators, and (3) only Ca2+-dependent inactivation was sensitive to compounds which alter the cytoskeleton. Drugs which stabilize (taxol and phalloidin) and destabilize (colchicine and cytochalasin B) the cytoskeleton altered the development and recovery from Ca2+-dependent inactivation, indicating that the neuronal cytoskeleton may mediate Ca2+ channel sensitivity to intracellular Ca2+. Ca2+-dependent inactivation was not associated with a particular subset of Ca2+ channels, suggesting that all Ca2+ channels in these neurons are inactivated by intracellular Ca2+.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adler EM, Augustine GJ, Duffy SN, Charlton MP (1991) Alien intracellular calcium chelators attenuate neurotransmitter release at the squid giant synapse. J Neurosci 11: 1496–1507

    PubMed  CAS  Google Scholar 

  2. Argibay JA, Fischmeister R, Hartzell HC (1988) Inactivation, reactivation and pacing dependence of calcium current in frog cardiocytes: correlation with current density. J Physiol (Lond) 401:201–226

    CAS  Google Scholar 

  3. Balke CW, Wier WG (1991) Ryanodine does not affect calcium current in guinea pig ventricular myocytes in which Ca2+ is buffered. Circ Res 68:897–902

    PubMed  CAS  Google Scholar 

  4. Bates SE, Gurney AM (1993) Ca2+ dependent block and potentiation of L-type calcium current in guinea-pig ventricular myocytes. J Physiol (Lond) 466:345–365

    CAS  Google Scholar 

  5. Brown AM, Schwindt PC, Crill WE (1993) Voltage dependence and activation kinetics of pharmacologically defined components of the high-threshold calcium current in rat neocortical neurons. J Neurophysiol 70:1530–1543

    PubMed  CAS  Google Scholar 

  6. Cantiello HF, Stow JL, Prat AG, Ausiello DA (1991) Actin filaments regulate epithelial Na+ channel activity. Am J Physiol 261:C882-C886

    PubMed  CAS  Google Scholar 

  7. Cantiello HF, Prat AG, Bonventre JV, Cunningham CC, Hartwig JH, Ausiello DA (1993) Actin-binding protein contributes to cell volume regulatory ion channel activation in melanoma cells. J Biol Chem 268:4596–4599

    PubMed  CAS  Google Scholar 

  8. Chad JE, Eckert R (1986) An enzymatic mechanism for calcium current inactivation in dialyzedHelix neurones. J Physiol (Lond) 378:31–51

    CAS  Google Scholar 

  9. Chad J, Eckert R, Ewald D (1984) Kinetics of calcium-dependent inactivation of calcium current in voltage-clamped neurones ofAplysia californica. J Physiol (Lond) 347:279–300

    CAS  Google Scholar 

  10. Cornet M, Ubl J, Kolb HA (1993) Cytoskeleton and ion movements during volume regulation in cultured PC12 cells. J Membr Biol 133:161–170

    PubMed  CAS  Google Scholar 

  11. Eckert R, Chad JE (1984) Inactivation of Ca2+ channels. Prog Biophys Mol Biol 44:215–267

    Article  PubMed  CAS  Google Scholar 

  12. Fryer MW, Zucker RS (1993) Ca2+-dependent inactivation of Ca2+ current inAplysia neurons: kinetic studies using photolabile Ca2+ chelators. J Physiol (Lond) 464:501–528

    CAS  Google Scholar 

  13. Fukuda J, Kameyama M, Yamaguchi K (1981) Breakdown of cytoskeletal filaments selectively reduces Na and Ca spikes in cultured neurones. Nature 294:82–85

    Article  PubMed  CAS  Google Scholar 

  14. Giannattasio B, Jones SW, Scarpa A (1991) Calcium currents in the A7r5 smooth muscle-derived cell line: calcium-dependent and voltage-dependent inactivation. J Gen Physiol 98: 987–1003

    Article  PubMed  CAS  Google Scholar 

  15. Gutnick MJ, Lux HD, Swandulla D, Zucker H (1989) Voltagedependent and calcium-dependent inactivation of calcium channel current in identified snail neurons. J Physiol (Lond) 412:197–220

    CAS  Google Scholar 

  16. Hadley RW, Lederer WJ (1991) Ca2+ and voltage inactivate Ca2+ channels in guinea-pig ventricular myocytes through independent mechanisms. J Physiol (Lond) 444:257–268

    CAS  Google Scholar 

  17. Imredy JP, Yue DT (1992) Submicroscopic Ca2+ diffusion mediates inhibitor coupling between individual Ca2+ channels. Neuron 9:197–207

    Article  PubMed  CAS  Google Scholar 

  18. Jmari K, Mironneau C, Mironneau J (1986) Inactivation of calcium channel current in rat uterine smooth muscle: evidence for calcium- and voltage-mediated mechanisms. J Physiol (Lond) 380:111–126

    CAS  Google Scholar 

  19. Johnson BD, Byerly L (1993) Photo-released intracellular Ca2+ rapidly blocks Ba2+ current inLymnaea neurons. J Physiol (Lond) 462:321–347

    CAS  Google Scholar 

  20. Johnson BD, Byerly L (1993) A cytoskeletal mechanism for Ca2+ channel metabolic dependence and inactivation by intracellular Ca2+. Neuron 10:797–804

    Article  PubMed  CAS  Google Scholar 

  21. Kasai H, Aosaki T (1988) Divalent cation dependent inactivation of the high-voltage-activated Ca2+-channel current in chick sensory neurons. Pflügers Arch 411:695–697

    Article  PubMed  CAS  Google Scholar 

  22. Kay AR (1991) Inactivation kinetics of calcium current of acutely dissociated CA1 pyramidal cells of the mature guineapig hippocampus. J Physiol (Lond) 437:27–48

    CAS  Google Scholar 

  23. Kay AR, Wong RKS (1986) Isolation of neurons suitable for patch-clamping from adult mammalian central nervous system. J Neurosci Methods 16:227–238

    Article  PubMed  CAS  Google Scholar 

  24. Keja JA, Stoof JC, Kits KS (1992) Dopamine D2 receptor stimulation differentially affects voltage-activated calcium channels in rat pituitary melanotropic cells. J Physiol (Lond) 450:409–435

    CAS  Google Scholar 

  25. Köhr G, Mody I (1991) Endogenous intracellular calcium buffering and the activation/inactivation of HVA calcium currents in rat dentate gyrus granule cells. J Gen Physiol 98:941–967

    Article  PubMed  Google Scholar 

  26. Kramer RH, Kaczmarek LK, Levitan ES (1991) Neuropeptide inhibition of voltage-gated calcium channels mediated by mobilization of intracellular calcium. Neuron 6:557–563

    Article  PubMed  CAS  Google Scholar 

  27. Li M, West JW, Lai Y, Scheuer T, Catterall WA (1992) Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8:1–20

    Article  Google Scholar 

  28. Matsumoto G, Sakai H (1979) Microtubules inside the plasma membrane of squid giant axons and their possible physiological function. J Membr Biol 50:1–14

    Article  PubMed  CAS  Google Scholar 

  29. Matsumoto G, Sakai H (1979) Restoration of membrane excitability of squid giant axons by reagents activating tyrosinetubulin ligase. J Membr Biol 50:15–22

    Article  PubMed  CAS  Google Scholar 

  30. Matsumoto G, Ichikawa M, Tasaki A (1984) Axonal microtubules necessary for generation of sodium current in squid giant axons: II. effect of colchicine upon asymmetrical displacement current. J Membr Biol 77:93–99

    PubMed  CAS  Google Scholar 

  31. Matsumoto G, Ichikawa M, Tasaki A, Murofushi H, Sakai H (1984) Axonal microtubules necessary for generation of sodium current in squid giant axons: I. pharmacological study on sodium current and restoration of sodium current by microtubule proteins and 260 K protein. J Membr Biol 77:77–91

    PubMed  CAS  Google Scholar 

  32. Mintz IM, Adams ME, Bean BP (1992) P-type calcium channels in rat central and peripheral neurons. Neuron 9:85–95

    Article  PubMed  CAS  Google Scholar 

  33. Morad M, Davies NW, Kaplan JH, Lux HD (1988) Inactivation and block of calcium channels by photo-released Ca2+ in dorsal root ganglion neurons. Science 241:842–844

    Article  PubMed  CAS  Google Scholar 

  34. Neher E (1986) Concentration profiles of intracellular calcium in the presence of a diffusible chelator. Exp Brain Res 14:80–96

    CAS  Google Scholar 

  35. Ohya Y, Kitamura K, Kuriyama H (1988) Regulation of calcium current by intracellular calcium in smooth muscle cells of rabbit portal vein. Circ Res 62:375–383

    PubMed  CAS  Google Scholar 

  36. Pelzer D, Pelzer S, McDonald TF (1990) Properties and regulation of calcium channels in muscle cells. Rev Physiol Biochem Pharmacol 114: 107–207

    Article  PubMed  CAS  Google Scholar 

  37. Peres A, Bertollini L, Camagni S, Wanke E (1991) [Ca2+]i recordings and the inactivation of the High-voltage-activated Ca2+ currents in the adult rat sensory neuron. Cell Calcium 12: 599–608

    Article  PubMed  CAS  Google Scholar 

  38. Pitler TA, Landfield PW (1987) Probable Ca2+-mediated inactivation of Ca2+ currents in mammalian neurons. Brain Res 410:147–153

    Article  PubMed  CAS  Google Scholar 

  39. Rosenmund C, Westbrook GL (1993) Calcium-induced actin depolymerization reduces NMDA channel activity. Neuron 10:805–814

    Article  PubMed  CAS  Google Scholar 

  40. Ruppersberg JP, Stocker M, Pongs O, Heinemann SH, Frank R, Koenen M (1991) Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation. Nature 352: 711–714

    Article  PubMed  CAS  Google Scholar 

  41. Schroeder JE, Fischbach PS, Mamo M, McClesky EW (1990) Two components of high-threshold Ca2+ current inactivate by different mechanisms. Neuron 5:445–452

    Article  PubMed  CAS  Google Scholar 

  42. Viana F, Bayliss DA, Berger AJ (1993) Calcium conductances and their role in the firing behavior of neonatal rat hypoglossal motoneurons. J Neurophysiol 69: 2137–2149

    PubMed  CAS  Google Scholar 

  43. Vreugdenhil M, Wadman WJ (1994) Kindling-induced long lasting enhancement of calcium current in hippocampal CA1 area of the rat: relation to calcium-dependent inactivation. Neuroscience 59:105–114

    Article  PubMed  CAS  Google Scholar 

  44. White E, Terrar DA (1992) Inactivation of Ca2+ current during the action potential in guinea-pig ventricular myocytes. Exp Physiol 77:153–164

    PubMed  CAS  Google Scholar 

  45. Yakel JL (1992) Inactivation of the Ba2+ current in dissociatedHelix neurons: voltage dependence and the role of phosphorylation. Pflügers Arch 420:470–478

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  47. Zeilhofer HU, Müller TH, Swandulla D (1993) Inhibition of high voltage-activated calcium currents by L-glutamate receptor-mediated calcium influx. Neuron 10:879–887

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Johnson, B.D., Byerly, L. Ca2+ channel Ca2+-dependent inactivation in a mammalian central neuron involves the cytoskeleton. Pflugers Arch. 429, 14–21 (1994). https://doi.org/10.1007/BF02584025

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02584025

Key words

Navigation