Skip to main content
SpringerLink
Log in

Monovalent Cations Contribute to T-type Calcium Channel (CaV3.1 and CaV3.2) Selectivity

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

Low voltage-activated (LVA) Ca2+ channels regulate chemical signaling by their ability to select for Ca2+. Whereas Ca2+ is the main permeating species through Ca2+ channels, Ca2+ permeation may be modified by abundant intra- and extracellular monovalent cations. Therefore, we explored monovalent cation regulation of LVA Ca2+ permeation in the cloned T-type Ca2+ channels α1G (CaV3.1) and α1H (CaV3.2). In physiological [Ca2+], the reversal potential in symmetrical Li+ was 19 mV in α1G and 18 mV in α1H, in symmetrical Cs+ the reversal potential was 36 mV in α1G and 37 mV in α1H, and in the bi-ionic condition with Li+ in the bath and Cs+ in the pipette, the reversal potential was 46 mV in both α1G and α1H. When Cs+ was used in the pipette, replacement of external Cs+ with Li+ (or Na+) shifted the reversal potential positive by 5–6 mV and increased the net inward current in α1G. Taken together the data indicate that in physiological [Ca2+], external Li+ (or Na+) permeates more readily than external Cs+, resulting in a positive shift of the reversal potential. We conclude that external monovalent cations dictate T-type Ca2+ channel selectivity by permeating through the channel. Similar to Li+, we previously reported that external [H+] can regulate T-type Ca2+ channel selectivity. α1H’s selectivity was more sensitive to external pH changes compared to α1G. When Cs+ was used in the pipette and Li+ was used in the bath external acidification from pHo 7.4 to 6.0 caused a negative shift of the reversal by 8 mV in α1H. Replacement of internal Cs+ with Li+ reduced the pH-induced shift of the reversal potential to 2 mV. We conclude that, similar to other external monovalent cations, H+ can modify T-type Ca2+ channel selectivity. However, in contrast to external monovalent ions that readily permeate, H+ regulate T-type Ca2+ channel selectivity by increasing the relative permeability of the internal monovalent cation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. B.P. Bean (1985) ArticleTitleTwo kinds of calcium channels in canine atrial cells: differences in kinetics, selectivity, and pharmacology. J. Gen. Physiol. 86 1–30 Occurrence Handle2411846

    PubMed  Google Scholar 

  2. D.E. Burgess O. Crawford B.P. Delisle J. Satin (2002) ArticleTitleMechanism of inactivation gating of human T-type (low-voltage activated) calcium channels. Biophys. J. 82 1894–1906 Occurrence Handle11916848

    PubMed  Google Scholar 

  3. E. Carbone H.D. Lux (1987) ArticleTitleKinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones. J. Physiol. 386 547–570 Occurrence Handle2445968

    PubMed  Google Scholar 

  4. L.L. Cribbs J.-H. Lee J. Yang J. Satin Y. Zhang A. Daud J. Barclay M.P. Williamson M. Fox M. Rees E. Perez-Reyes (1998) ArticleTitleCloning and characterization of α1H from human heart, a member of the T-type calcium channel gene family. Circ. Res. 83 103–109 Occurrence Handle9670923

    PubMed  Google Scholar 

  5. T.X. Dang E.W. McCleskey (1998) ArticleTitleIon channel selectivity through stepwise changes in binding affinity. J. Gen. Physiol. 111 185–193 Occurrence Handle10.1085/jgp.111.2.185 Occurrence Handle9450938

    Article  PubMed  Google Scholar 

  6. B.P. Delisle J. Satin (2000) ArticleTitlepH Modification of human T-type calcium channel gating. Biophys. J. 78 1895–1905 Occurrence Handle10733969

    PubMed  Google Scholar 

  7. E.A. Ertel K.P. Campbell M.M. Harpold F. Hofmann Y. Mori E. Perez-Reyes A. Schwartz T.P. Snutch T. Tanabe L. Birnbaumer R.W. Tsien W.A. Catterall (2000) ArticleTitleNomenclature of voltage-gated calcium channels. Neuron 25 533–535 Occurrence Handle1:CAS:528:DC%2BD3cXisFKrtL0%3D Occurrence Handle10774722

    CAS  PubMed  Google Scholar 

  8. Y. Fukushima S. Hagiwara (1985) ArticleTitleCurrents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes. J. Physiol. 358 255–284 Occurrence Handle2580082

    PubMed  Google Scholar 

  9. P. Hess J.B. Lansman R.W. Tsien (1986) ArticleTitleCalcium channel selectivity for divalent and monovalent cations: voltage and concentration dependence of single channel current in ventricular heart cells. J. Gen. Physiol. 88 293–319 Occurrence Handle2428919

    PubMed  Google Scholar 

  10. B. Hille (2001) Ion Channels of Excitable Membranes. Sinauer Associates, Inc. Sunderland, MA

    Google Scholar 

  11. J.R. Huguenard (1996) ArticleTitleLow-threshold calcium currents in central nervous system neurons. Annu. Rev. Physiol. 58 329–348 Occurrence Handle10.1146/annurev.ph.58.030196.001553 Occurrence Handle8815798

    Article  PubMed  Google Scholar 

  12. C.C. Kuo P. Hess (1993a) ArticleTitleBlock of the L-type Ca2+ channel pore by external and internal Mg2+ in rat phaeochromocytoma cells. J. Physiol. 466 683–706

    Google Scholar 

  13. C.C. Kuo P. Hess (1993b) ArticleTitleCharacterization of the high-affinity Ca2+ binding sites on the L-type Ca2+ channel pore in rat phaeochromocytoma cells. J. Physiol. 466 657–682

    Google Scholar 

  14. C.C. Kuo P. Hess (1993c) ArticleTitleIon permeation through the L-type Ca2+ channel in rat phaeochromocytoma cells: Two sets of ion binding sites in the pore. J. Physiol. 466 629–655 Occurrence Handle1:CAS:528:DyaK3sXksVKhs7o%3D

    CAS  Google Scholar 

  15. Y.W. Kwan R.S. Kass (1993) ArticleTitleInteractions between protons and calcium near L-type calcium channels: Evidence for independent channel-associated binding sites. Biophys. J. 65 1188–1195 Occurrence Handle1:CAS:528:DyaK2cXhtVaru7g%3D Occurrence Handle8241399

    CAS  PubMed  Google Scholar 

  16. J.-H. Lee J.C. Gomora L.L. Cribbs E. Perez-Reyes (1999) ArticleTitleNickel block of three cloned T-type calcium channels: Low concentrations selectively block alpha 1H. Biophys. J. 77 3034–3042 Occurrence Handle1:CAS:528:DyaK1MXotVGhsLc%3D Occurrence Handle10585925

    CAS  PubMed  Google Scholar 

  17. E.W. McCleskey W. Almers (1985) ArticleTitleThe Ca channel in skeletal muscle is a large pore. Proc. Natl. Acad. Sci. USA 82 7149–7153 Occurrence Handle1:STN:280:BimD3MnosFY%3D Occurrence Handle2413461

    CAS  PubMed  Google Scholar 

  18. D. Pietrobon B. Prod’hom P. Hess (1989) ArticleTitleInteractions of protons with single open L-type calcium channels. J. Gen. Physiol. 94 1–21 Occurrence Handle1:STN:280:By%2BD3sbisVM%3D Occurrence Handle2553855

    CAS  PubMed  Google Scholar 

  19. L. Polo-Parada S.J. Korn (1997) ArticleTitleBlock of N-type calcium channels in chick sensory neurons by external sodium. J. Gen. Physiol. 109 693–702 Occurrence Handle10.1085/jgp.109.6.693 Occurrence Handle1:CAS:528:DyaK2sXktFaqtrk%3D Occurrence Handle9222896

    Article  CAS  PubMed  Google Scholar 

  20. B. Prod’hom D. Pietrobon P. Hess (1989) ArticleTitleInteractions of protons with single open L-type calcium channels. Location of protonation site and dependence of proton-induced current fluctuations on concentration and species of permeant ion. J. Gen. Physiol. 94 23–42 Occurrence Handle1:STN:280:By%2BD3sbisFY%3D Occurrence Handle2553858

    CAS  PubMed  Google Scholar 

  21. J. Satin L.L. Cribbs (2000) ArticleTitleIdentification of a T-type calcium channel isoform in murine atrial myocytes (AT-1). Circ. Res. 86 636–642 Occurrence Handle1:CAS:528:DC%2BD3cXitlajsbg%3D Occurrence Handle10746998

    CAS  PubMed  Google Scholar 

  22. G.C. Tombough G.G. Somjen (1996) ArticleTitleEffects of extracellular pH on voltage gated Na, K, and Ca currents in isolated rat CA1 neurons. J. Physiol. 493 719–732 Occurrence Handle8799894

    PubMed  Google Scholar 

  23. R.W. Tsien P. Hess E.W. McCleksky R.L. Rosenberg (1987) ArticleTitleCalcium channels: Mechanisms of selectivity, permeation, and block. Annu. Rev. Biophys. Biophys. Chem. 16 265–290 Occurrence Handle10.1146/annurev.bb.16.060187.001405 Occurrence Handle1:CAS:528:DyaL2sXltFWitbc%3D Occurrence Handle2439098

    Article  CAS  PubMed  Google Scholar 

  24. R.W. Tsien D. Lipscombe D.V. Madison K.R. Bley A.P. Fox (1988) ArticleTitleMultiple types of neuronal calcium channels and their selective modulation. Trends Neurosci. 11 431–438 Occurrence Handle10.1016/0166-2236(88)90194-4 Occurrence Handle1:STN:280:BiaB38zgslI%3D Occurrence Handle2469160

    Article  CAS  PubMed  Google Scholar 

  25. J. Tytgat B. Nilius E. Carmeliet (1990) ArticleTitleModulation of the T-type cardiac Ca channel by changes in proton concentration. J. Gen. Physiol. 96 973–990 Occurrence Handle1:STN:280:By6C38zpvFc%3D Occurrence Handle2177772

    CAS  PubMed  Google Scholar 

  26. N. Yamashita S. Ciani S. Hagiwara (1990) ArticleTitleEffects of internal Na on the Ca channel outward current in mouse neoplastic B lymphocytes. J. Gen. Physiol 96 559–579 Occurrence Handle1:STN:280:By6D3sjpt1Q%3D Occurrence Handle2172442

    CAS  PubMed  Google Scholar 

  27. Y. Zhang L.L. Cribbs J. Satin (2000) ArticleTitleArachidonic acid modulation of α1H, a cloned human T-type calcium channel. Amer. J. Physiol. 278 H184–H193 Occurrence Handle1:CAS:528:DC%2BD3cXht1Ght7k%3D

    CAS  Google Scholar 

  28. Y. Zhang M. Mori D.L. Burgess J.L. Noebels (2002) ArticleTitleMutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J. Neurosci. 22 6362–6371 Occurrence Handle1:CAS:528:DC%2BD38XlvFKns7g%3D Occurrence Handle12151514

    CAS  PubMed  Google Scholar 

  29. W. Zhou S. Jones (1996) ArticleTitleThe effects of external pH on calcium channel currents in bullfrog sympathetic neurons. Biophys. J. 70 1326–1334 Occurrence Handle1:CAS:528:DyaK28XitVOgsb8%3D Occurrence Handle8785288

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to the continuing support with cells and clones by Dr. L.L. Cribbs (Loyola). Supported by NIH HL-63416 (J.S.). JS is an Established Investigator of the American Heart Association.

Author information

Authors and Affiliations

  1. Department of Physiology, The University of Kentucky College Medicine, 800 Rose St., Lexington, KY 40536-0298, USA

    B. P. Delisle & J. Satin

Authors
  1. B. P. Delisle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Satin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Satin.

Additional information

Present address: B.P. Delisle, Department of Medicine, The University of Wisconsin, Madison, WI 53706, USA

Rights and permissions

Reprints and permissions

About this article

Cite this article

Delisle, B., Satin, J. Monovalent Cations Contribute to T-type Calcium Channel (CaV3.1 and CaV3.2) Selectivity . J. Membrane Biol. 193, 185–194 (2003). https://doi.org/10.1007/s00232-003-2017-9

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-003-2017-9

Keywords

Search

Navigation