Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1996 Dec 15;497(Pt 3):675–686. doi: 10.1113/jphysiol.1996.sp021799

Coupling between charge movement and pore opening in vertebrate neuronal alpha 1E calcium channels.

R Olcese 1, A Neely 1, N Qin 1, X Wei 1, L Birnbaumer 1, E Stefani 1
PMCID: PMC1160964  PMID: 9003553

Abstract

1. Neuronal alpha 1E Ca2+ channels were expressed alone and in combination with the beta 2a subunit in Xenopus laevis oocytes. 2. The properties of ionic and gating currents of alpha 1E were investigated: ionic currents were measured in 10 mM external Ba2+; gating currents were isolated in 2 mM external Co2+. 3. Charge movement preceded channel opening. The charge movement voltage curve (Q(V)) preceded the ionic conductance voltage dependence (G(V)) by approximately 20 mV. 4. Coexpression of alpha 1E with the beta 2a subunit did not modify the voltage dependence of charge movement but shifted the G(V) curve to more negative potentials. The voltage gap between Q(V) and G(V) curves was reduced by the beta 2a subunit and both curves overlapped at potentials near 0 mV. 5. The coupling efficiency between the charge movement and pore opening was estimated by the ration between limiting conductance and maximum charge movement (Gmax/Qmax). Coexpression of the beta 2a subunit increased the Gmax/Qmax ratio from 9.2 x 10(5) +/- 1.4 x 10(5) to 21.9 x 10(5) +/- 2.8 X 10(5) S C-1 for alpha 1E and alpha 1E + beta 2a, respectively. 6. We conclude that in the neuronal alpha 1E the charge movement is tightly coupled with the pore opening and that the beta 2a subunit coexpression further improves this coupling.

Full text

PDF
675

Selected References

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

  1. Almers W., Armstrong C. M. Survival of K+ permeability and gating currents in squid axons perfused with K+-free media. J Gen Physiol. 1980 Jan;75(1):61–78. doi: 10.1085/jgp.75.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barish M. E. A transient calcium-dependent chloride current in the immature Xenopus oocyte. J Physiol. 1983 Sep;342:309–325. doi: 10.1113/jphysiol.1983.sp014852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bean B. P., Rios E. Nonlinear charge movement in mammalian cardiac ventricular cells. Components from Na and Ca channel gating. J Gen Physiol. 1989 Jul;94(1):65–93. doi: 10.1085/jgp.94.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Catterall W. A. Functional subunit structure of voltage-gated calcium channels. Science. 1991 Sep 27;253(5027):1499–1500. doi: 10.1126/science.1654596. [DOI] [PubMed] [Google Scholar]
  5. De Waard M., Campbell K. P. Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus oocytes. J Physiol. 1995 Jun 15;485(Pt 3):619–634. doi: 10.1113/jphysiol.1995.sp020757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hofmann F., Biel M., Flockerzi V. Molecular basis for Ca2+ channel diversity. Annu Rev Neurosci. 1994;17:399–418. doi: 10.1146/annurev.ne.17.030194.002151. [DOI] [PubMed] [Google Scholar]
  7. Hullin R., Singer-Lahat D., Freichel M., Biel M., Dascal N., Hofmann F., Flockerzi V. Calcium channel beta subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J. 1992 Mar;11(3):885–890. doi: 10.1002/j.1460-2075.1992.tb05126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Josephson I. R., Varadi G. The beta subunit increases Ca2+ currents and gating charge movements of human cardiac L-type Ca2+ channels. Biophys J. 1996 Mar;70(3):1285–1293. doi: 10.1016/S0006-3495(96)79685-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kamp T. J., Pérez-García M. T., Marban E. Enhancement of ionic current and charge movement by coexpression of calcium channel beta 1A subunit with alpha 1C subunit in a human embryonic kidney cell line. J Physiol. 1996 Apr 1;492(Pt 1):89–96. doi: 10.1113/jphysiol.1996.sp021291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lacerda A. E., Kim H. S., Ruth P., Perez-Reyes E., Flockerzi V., Hofmann F., Birnbaumer L., Brown A. M. Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel. Nature. 1991 Aug 8;352(6335):527–530. doi: 10.1038/352527a0. [DOI] [PubMed] [Google Scholar]
  11. Lee K. S., Tsien R. W. Reversal of current through calcium channels in dialysed single heart cells. Nature. 1982 Jun 10;297(5866):498–501. doi: 10.1038/297498a0. [DOI] [PubMed] [Google Scholar]
  12. Lory P., Varadi G., Slish D. F., Varadi M., Schwartz A. Characterization of beta subunit modulation of a rabbit cardiac L-type Ca2+ channel alpha 1 subunit as expressed in mouse L cells. FEBS Lett. 1993 Jan 4;315(2):167–172. doi: 10.1016/0014-5793(93)81156-t. [DOI] [PubMed] [Google Scholar]
  13. Mannuzzu L. M., Moronne M. M., Isacoff E. Y. Direct physical measure of conformational rearrangement underlying potassium channel gating. Science. 1996 Jan 12;271(5246):213–216. doi: 10.1126/science.271.5246.213. [DOI] [PubMed] [Google Scholar]
  14. Neely A., Olcese R., Wei X., Birnbaumer L., Stefani E. Ca(2+)-dependent inactivation of a cloned cardiac Ca2+ channel alpha 1 subunit (alpha 1C) expressed in Xenopus oocytes. Biophys J. 1994 Jun;66(6):1895–1903. doi: 10.1016/S0006-3495(94)80983-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Neely A., Wei X., Olcese R., Birnbaumer L., Stefani E. Potentiation by the beta subunit of the ratio of the ionic current to the charge movement in the cardiac calcium channel. Science. 1993 Oct 22;262(5133):575–578. doi: 10.1126/science.8211185. [DOI] [PubMed] [Google Scholar]
  16. Nishimura S., Takeshima H., Hofmann F., Flockerzi V., Imoto K. Requirement of the calcium channel beta subunit for functional conformation. FEBS Lett. 1993 Jun 21;324(3):283–286. doi: 10.1016/0014-5793(93)80135-h. [DOI] [PubMed] [Google Scholar]
  17. Noceti F., Baldelli P., Wei X., Qin N., Toro L., Birnbaumer L., Stefani E. Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels. J Gen Physiol. 1996 Sep;108(3):143–155. doi: 10.1085/jgp.108.3.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Olcese R., Qin N., Schneider T., Neely A., Wei X., Stefani E., Birnbaumer L. The amino terminus of a calcium channel beta subunit sets rates of channel inactivation independently of the subunit's effect on activation. Neuron. 1994 Dec;13(6):1433–1438. doi: 10.1016/0896-6273(94)90428-6. [DOI] [PubMed] [Google Scholar]
  19. Perez-Reyes E., Castellano A., Kim H. S., Bertrand P., Baggstrom E., Lacerda A. E., Wei X. Y., Birnbaumer L. Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel. J Biol Chem. 1992 Jan 25;267(3):1792–1797. [PubMed] [Google Scholar]
  20. Perez-Reyes E., Kim H. S., Lacerda A. E., Horne W., Wei X. Y., Rampe D., Campbell K. P., Brown A. M., Birnbaumer L. Induction of calcium currents by the expression of the alpha 1-subunit of the dihydropyridine receptor from skeletal muscle. Nature. 1989 Jul 20;340(6230):233–236. doi: 10.1038/340233a0. [DOI] [PubMed] [Google Scholar]
  21. Pérez-García M. T., Kamp T. J., Marbán E. Functional properties of cardiac L-type calcium channels transiently expressed in HEK293 cells. Roles of alpha 1 and beta subunits. J Gen Physiol. 1995 Feb;105(2):289–305. doi: 10.1085/jgp.105.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rakowski R. F. Charge movement by the Na/K pump in Xenopus oocytes. J Gen Physiol. 1993 Jan;101(1):117–144. doi: 10.1085/jgp.101.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sanford J., Codina J., Birnbaumer L. Gamma-subunits of G proteins, but not their alpha- or beta-subunits, are polyisoprenylated. Studies on post-translational modifications using in vitro translation with rabbit reticulocyte lysates. J Biol Chem. 1991 May 25;266(15):9570–9579. [PubMed] [Google Scholar]
  24. Schneider T., Wei X., Olcese R., Costantin J. L., Neely A., Palade P., Perez-Reyes E., Qin N., Zhou J., Crawford G. D. Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit. Receptors Channels. 1994;2(4):255–270. [PubMed] [Google Scholar]
  25. Schoppa N. E., McCormack K., Tanouye M. A., Sigworth F. J. The size of gating charge in wild-type and mutant Shaker potassium channels. Science. 1992 Mar 27;255(5052):1712–1715. doi: 10.1126/science.1553560. [DOI] [PubMed] [Google Scholar]
  26. Shistik E., Ivanina T., Puri T., Hosey M., Dascal N. Ca2+ current enhancement by alpha 2/delta and beta subunits in Xenopus oocytes: contribution of changes in channel gating and alpha 1 protein level. J Physiol. 1995 Nov 15;489(Pt 1):55–62. doi: 10.1113/jphysiol.1995.sp021029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Singer D., Biel M., Lotan I., Flockerzi V., Hofmann F., Dascal N. The roles of the subunits in the function of the calcium channel. Science. 1991 Sep 27;253(5027):1553–1557. doi: 10.1126/science.1716787. [DOI] [PubMed] [Google Scholar]
  28. Stea A., Dubel S. J., Pragnell M., Leonard J. P., Campbell K. P., Snutch T. P. A beta-subunit normalizes the electrophysiological properties of a cloned N-type Ca2+ channel alpha 1-subunit. Neuropharmacology. 1993 Nov;32(11):1103–1116. doi: 10.1016/0028-3908(93)90005-n. [DOI] [PubMed] [Google Scholar]
  29. Stefani E., Toro L., Perozo E., Bezanilla F. Gating of Shaker K+ channels: I. Ionic and gating currents. Biophys J. 1994 Apr;66(4):996–1010. doi: 10.1016/S0006-3495(94)80881-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Varadi G., Lory P., Schultz D., Varadi M., Schwartz A. Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel. Nature. 1991 Jul 11;352(6331):159–162. doi: 10.1038/352159a0. [DOI] [PubMed] [Google Scholar]
  31. Wei X. Y., Perez-Reyes E., Lacerda A. E., Schuster G., Brown A. M., Birnbaumer L. Heterologous regulation of the cardiac Ca2+ channel alpha 1 subunit by skeletal muscle beta and gamma subunits. Implications for the structure of cardiac L-type Ca2+ channels. J Biol Chem. 1991 Nov 15;266(32):21943–21947. [PubMed] [Google Scholar]
  32. Williams M. E., Feldman D. H., McCue A. F., Brenner R., Velicelebi G., Ellis S. B., Harpold M. M. Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992 Jan;8(1):71–84. doi: 10.1016/0896-6273(92)90109-q. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES