Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 1996 Aug;71(2):787–794. doi: 10.1016/S0006-3495(96)79278-0

Conductance and permeation of monovalent cations through depletion-activated Ca2+ channels (ICRAC) in Jurkat T cells.

A Lepple-Wienhues 1, M D Cahalan 1
PMCID: PMC1233535  PMID: 8842217

Abstract

We studied monovalent permeability of Ca2+ release-activated Ca2+ channels (ICRAC) in Jurkat T lymphocytes following depletion of calcium stores. When external free Ca2+ ([Ca2+]o) was reduced to micromolar levels in the absence of Mg2+, the inward current transiently decreased and then increased approximately sixfold, accompanied by visibly enhanced current noise. The monovalent currents showed a characteristically slow deactivation (tau = 3.8 and 21.6 s). The extent of Na+ current deactivation correlated with the instantaneous Ca2+ current upon readdition of [Ca2+]o. No conductance increase was seen when [Ca2+]o was reduced before activation of ICRAC. With Na+ outside and Cs+ inside, the current rectified inwardly without apparent reversal below 40 mV. The sequence of conductance determined from the inward current at -80 mV was Na+ > Li+ = K+ > Rb+ >> Cs+. Unitary inward conductance of the Na+ current was 2.6 pS, estimated from the ratios delta sigma2/delta Imean at different voltages. External Ca2+ blocked the Na+ current reversibly with an IC50 value of 4 microM. Na+ currents were also blocked by 3 mM Mg2+ or 10 microM La3+. We conclude that ICRAC channels become permeable to monovalent cations at low levels of external divalent ions. In contrast to voltage-activated Ca2+ channels, the monovalent conductance is highly selective for Na+ over Cs+. Na+ currents through ICRAC channels provide a means to study channel characteristics in an amplified current model.

Full text

PDF
794

Selected References

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

  1. Almers W., McCleskey E. W., Palade P. T. A non-selective cation conductance in frog muscle membrane blocked by micromolar external calcium ions. J Physiol. 1984 Aug;353:565–583. doi: 10.1113/jphysiol.1984.sp015351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ellinor P. T., Yang J., Sather W. A., Zhang J. F., Tsien R. W. Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions. Neuron. 1995 Nov;15(5):1121–1132. doi: 10.1016/0896-6273(95)90100-0. [DOI] [PubMed] [Google Scholar]
  3. Fasolato C., Hoth M., Penner R. A GTP-dependent step in the activation mechanism of capacitative calcium influx. J Biol Chem. 1993 Oct 5;268(28):20737–20740. [PubMed] [Google Scholar]
  4. Fasolato C., Innocenti B., Pozzan T. Receptor-activated Ca2+ influx: how many mechanisms for how many channels? Trends Pharmacol Sci. 1994 Mar;15(3):77–83. doi: 10.1016/0165-6147(94)90282-8. [DOI] [PubMed] [Google Scholar]
  5. Fukushima Y., Hagiwara S. Currents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes. J Physiol. 1985 Jan;358:255–284. doi: 10.1113/jphysiol.1985.sp015550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hess P., Lansman J. B., Tsien R. W. Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol. 1986 Sep;88(3):293–319. doi: 10.1085/jgp.88.3.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hess P., Tsien R. W. Mechanism of ion permeation through calcium channels. 1984 May 31-Jun 6Nature. 309(5967):453–456. doi: 10.1038/309453a0. [DOI] [PubMed] [Google Scholar]
  8. Hoth M. Calcium and barium permeation through calcium release-activated calcium (CRAC) channels. Pflugers Arch. 1995 Jul;430(3):315–322. doi: 10.1007/BF00373905. [DOI] [PubMed] [Google Scholar]
  9. Hoth M., Penner R. Calcium release-activated calcium current in rat mast cells. J Physiol. 1993 Jun;465:359–386. doi: 10.1113/jphysiol.1993.sp019681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoth M., Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature. 1992 Jan 23;355(6358):353–356. doi: 10.1038/355353a0. [DOI] [PubMed] [Google Scholar]
  11. Lewis R. S., Cahalan M. D. Mitogen-induced oscillations of cytosolic Ca2+ and transmembrane Ca2+ current in human leukemic T cells. Cell Regul. 1989 Nov;1(1):99–112. doi: 10.1091/mbc.1.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lewis R. S., Cahalan M. D. Potassium and calcium channels in lymphocytes. Annu Rev Immunol. 1995;13:623–653. doi: 10.1146/annurev.iy.13.040195.003203. [DOI] [PubMed] [Google Scholar]
  13. Lückhoff A., Clapham D. E. Calcium channels activated by depletion of internal calcium stores in A431 cells. Biophys J. 1994 Jul;67(1):177–182. doi: 10.1016/S0006-3495(94)80467-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McCleskey E. W., Almers W. The Ca channel in skeletal muscle is a large pore. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7149–7153. doi: 10.1073/pnas.82.20.7149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McDonald T. V., Premack B. A., Gardner P. Flash photolysis of caged inositol 1,4,5-trisphosphate activates plasma membrane calcium current in human T cells. J Biol Chem. 1993 Feb 25;268(6):3889–3896. [PubMed] [Google Scholar]
  16. Negulescu P. A., Shastri N., Cahalan M. D. Intracellular calcium dependence of gene expression in single T lymphocytes. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2873–2877. doi: 10.1073/pnas.91.7.2873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Neher E. The influence of intracellular calcium concentration on degranulation of dialysed mast cells from rat peritoneum. J Physiol. 1988 Jan;395:193–214. doi: 10.1113/jphysiol.1988.sp016914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Parekh A. B., Penner R. Depletion-activated calcium current is inhibited by protein kinase in RBL-2H3 cells. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7907–7911. doi: 10.1073/pnas.92.17.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parekh A. B., Terlau H., Stühmer W. Depletion of InsP3 stores activates a Ca2+ and K+ current by means of a phosphatase and a diffusible messenger. Nature. 1993 Aug 26;364(6440):814–818. doi: 10.1038/364814a0. [DOI] [PubMed] [Google Scholar]
  20. Premack B. A., McDonald T. V., Gardner P. Activation of Ca2+ current in Jurkat T cells following the depletion of Ca2+ stores by microsomal Ca(2+)-ATPase inhibitors. J Immunol. 1994 Jun 1;152(11):5226–5240. [PubMed] [Google Scholar]
  21. Randriamampita C., Tsien R. Y. Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature. 1993 Aug 26;364(6440):809–814. doi: 10.1038/364809a0. [DOI] [PubMed] [Google Scholar]
  22. Ross P. E., Cahalan M. D. Ca2+ influx pathways mediated by swelling or stores depletion in mouse thymocytes. J Gen Physiol. 1995 Sep;106(3):415–444. doi: 10.1085/jgp.106.3.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Somasundaram B., Norman J. C., Mahaut-Smith M. P. Primaquine, an inhibitor of vesicular transport, blocks the calcium-release-activated current in rat megakaryocytes. Biochem J. 1995 Aug 1;309(Pt 3):725–729. doi: 10.1042/bj3090725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vaca L., Kunze D. L. Depletion of intracellular Ca2+ stores activates a Ca(2+)-selective channel in vascular endothelium. Am J Physiol. 1994 Oct;267(4 Pt 1):C920–C925. doi: 10.1152/ajpcell.1994.267.4.C920. [DOI] [PubMed] [Google Scholar]
  25. Zhang L., McCloskey M. A. Immunoglobulin E receptor-activated calcium conductance in rat mast cells. J Physiol. 1995 Feb 15;483(Pt 1):59–66. doi: 10.1113/jphysiol.1995.sp020567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zweifach A., Lewis R. S. Calcium-dependent potentiation of store-operated calcium channels in T lymphocytes. J Gen Physiol. 1996 May;107(5):597–610. doi: 10.1085/jgp.107.5.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zweifach A., Lewis R. S. Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295–6299. doi: 10.1073/pnas.90.13.6295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zweifach A., Lewis R. S. Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback. J Gen Physiol. 1995 Feb;105(2):209–226. doi: 10.1085/jgp.105.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zweifach A., Lewis R. S. Slow calcium-dependent inactivation of depletion-activated calcium current. Store-dependent and -independent mechanisms. J Biol Chem. 1995 Jun 16;270(24):14445–14451. doi: 10.1074/jbc.270.24.14445. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES