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The Human Red Cell Voltage-regulated Cation Channel. The Interplay with the Chloride Conductance, the Ca2+-activated K+ Channel and the Ca2+ Pump

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Abstract

The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was slow (t 1/2 about 30 s), whereas the deactivation was fast (t 1/2 about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl− concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gárdos channel elicited by Ca2+ influx via the cation channel and ensuing efflux via the Ca2+ pump. Thus, the voltage-dependent cation channel, the Gárdos channel and the Ca2+ pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.

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References

  1. J.S. Adorante R.I. Macey (1986) ArticleTitleCalcium-induced transient potassium efflux in human red blood cells. Am. J. Physiol. 250 C55–C64 Occurrence Handle1:CAS:528:DyaL28Xos1Sntw%3D%3D Occurrence Handle3079961

    CAS  PubMed  Google Scholar 

  2. P. Bennekou (1984) ArticleTitleK+-valinomycin and chloride conductance of the human red cell membrane. Influence of the membrane protonophore carbonylcyanide m-chlorophenylhydrazone. Biochim. Biophys. Acta 776 1–9 Occurrence Handle1:CAS:528:DyaL2cXls1GqsrY%3D Occurrence Handle6477898

    CAS  PubMed  Google Scholar 

  3. P. Bennekou (1988) ArticleTitleProtonophore anion permeability of the human red cell membrane determined in the presence of valinomycin. J. Membrane Biol. 102 225–234 Occurrence Handle1:CAS:528:DyaL1cXkvFSgsLg%3D

    CAS  Google Scholar 

  4. P. Bennekou (1993) ArticleTitleThe voltage-gated non-selective cation channel from human red cells is sensitive to acetylcholine. Biochim. Biophys. Acta 1147 165–167 Occurrence Handle1:CAS:528:DyaK3sXit1Kgsr8%3D Occurrence Handle7682111

    CAS  PubMed  Google Scholar 

  5. P. Bennekou (1999) ArticleTitleThe feasibility of pharmacological volume control of sickle cells is dependent on the quantization of the transport pathways. A model study. J. Theor. Biol. 196 129–137 Occurrence Handle1:CAS:528:DyaK1MXhtVejsrk%3D Occurrence Handle9892561

    CAS  PubMed  Google Scholar 

  6. P. Bennekou P. Christophersen (1992) ArticleTitleA human red cell cation channel showing hysteresis like voltage activation/inactivation. Acta Physiol. Scand. 146 Sup 608 56

    Google Scholar 

  7. P. Bennekou O. Pedersen A. Møller P. Christophersen (2000) ArticleTitleVolume control in sickle cells is facilitated by the novel anion conductance inhibitor NS1652. Blood 95 1842–1849 Occurrence Handle1:CAS:528:DC%2BD3cXhsVGgu7w%3D Occurrence Handle10688846

    CAS  PubMed  Google Scholar 

  8. P. Christophersen P. Bennekou (1991) ArticleTitleEvidence for a voltage-gated, non-selective cation channel in the human red cell membrane. Biochim. Biophys. Acta 1065 103–106 Occurrence Handle1:CAS:528:DyaK3MXksVKlu7s%3D Occurrence Handle1710495

    CAS  PubMed  Google Scholar 

  9. H. Dawson (1939) ArticleTitleStudies on the permeability of erythrocytes. VI. The effect of reducing the salt concentration in the medium surrounding the cell. Biochem. J. 33 389–401

    Google Scholar 

  10. A.J. Donlon A. Rothstein (1969) ArticleTitleThe cation permeability of erythrocytes in low ionic strength media of various tonicities. J. Membrane Biol. 1 37–52 Occurrence Handle1:CAS:528:DyaE3cXksVaqsbo%3D

    CAS  Google Scholar 

  11. C. Duranton S.M. Huber F. Lang (2002) ArticleTitleOxidation induces a Cl−-dependent cation conductance in human red blood cells. J. Physiol. 539 847–855 Occurrence Handle1:CAS:528:DC%2BD38Xjt1ejs7o%3D Occurrence Handle11897854

    CAS  PubMed  Google Scholar 

  12. CM Fanger S Ghanshani NJ Logsdon H Rauer K Kalman J Zhou K Beckingham KE Chandy MD Cahalan J Aiyar (1999) ArticleTitleCalmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J. Biol. Chem. 274 5746–5754 Occurrence Handle1:CAS:528:DyaK1MXhsFejtrs%3D Occurrence Handle10026195

    CAS  PubMed  Google Scholar 

  13. Fomenti, A., Rodighiero, S. 2001. Whole-cell and perforated-patch recordings of voltage-dependent outward and inward cation currents in human red blood cells. XIII Meeting of the European Association for Red Cell Research. 72

  14. J.C. Freedman J.F. Hoffman (1979) ArticleTitleIonic and osmotic equilibria of human red blood cells treated with nystatin. J. Gen. Physiol. 74 157–185 Occurrence Handle490141

    PubMed  Google Scholar 

  15. J.A. Halperin C. Brugnara M.T. Tosteson T. Van Ha D.C. Tosteson (1989) ArticleTitleVoltage-activated cation transport in human erythrocytes. Am. J. Physiol. 257 C986–C996 Occurrence Handle1:CAS:528:DyaK3cXjtlyksA%3D%3D Occurrence Handle2596592

    CAS  PubMed  Google Scholar 

  16. J.A. Halperin C. Brugnara T. van Ha D.C. Tosteson (1990) ArticleTitleVoltage-activated cation permeability in high-potassium but no low-potassium red blood cells. Am. J. Physiol. 258 C1169–C1172 Occurrence Handle1:STN:280:By%2BB1MjhvFY%3D Occurrence Handle1694398

    CAS  PubMed  Google Scholar 

  17. A. Heinz H. Passow (1980) ArticleTitleRole of external potassium in the calcium-induced potassium efflux from human red blood cell ghosts. J. Membr. Biol. 57 IssueID2 119–131 Occurrence Handle1:CAS:528:DyaL3MXhtVSmu74%3D Occurrence Handle6259362

    CAS  PubMed  Google Scholar 

  18. A.L. Hodgkin A.F. Huxley (1952) ArticleTitleThe components of membrane conductance in the giant axon of Loligo. J. Physiol. 116 449–472

    Google Scholar 

  19. S.M. Huber N. Gamper F. Lang (2001) ArticleTitleChloride conductance and volume-regulatory nonselective cation conductance in human red blood cell ghosts. Pfluegers Arch. - Eur. J. Physiol. 441 551–558 Occurrence Handle1:CAS:528:DC%2BD3MXlt1Ogtw%3D%3D

    CAS  Google Scholar 

  20. G.S. Jones P.A. Knauf (1985) ArticleTitleMechanism of the increase in cation permeability of human erythrocytes in low-chloride media. J. Gen. Physiol. 86 721–738 Occurrence Handle1:CAS:528:DyaL2MXmtFaiur4%3D Occurrence Handle4067572

    CAS  PubMed  Google Scholar 

  21. L. Kaestner P. Christophersen I. Bernhardt P. Bennekou (2001) ArticleTitleThe non-selective voltage-activated cation channel in the human red blood cell membrane: Reconciliation between two conflicting reports and further characterization. Biolectrichemistry 52 117–125

    Google Scholar 

  22. D. Kummerow J. Hamann J.A. Browning R. Wilkins J.C. Ellory I. Bernhardt (2000) ArticleTitleVariations of intracellular pH in human erythrocytes via K+(Na+)/H+ exchange under low ionic strength conditions. J. Membrane Biol. 176 207–216 Occurrence Handle1:CAS:528:DC%2BD3cXmtFCqu7w%3D

    CAS  Google Scholar 

  23. P.L. LaCelle A. Rothstein (1966) ArticleTitleThe passive permeability of the red blood cell to cations. J. Gen. Physiol. 50 171–189 Occurrence Handle1:CAS:528:DyaF2sXkvVyrsr4%3D Occurrence Handle5971026

    CAS  PubMed  Google Scholar 

  24. S. Richter J. Hamann D. Kummerow I. Bernhardt (1997) ArticleTitleThe monovalent cation ‘leak’ transport in human erythrocytes: An electroneutral exchange process. Biophys. J. 73 733–745 Occurrence Handle1:CAS:528:DyaK2sXkvFCmurk%3D Occurrence Handle9251790

    CAS  PubMed  Google Scholar 

  25. O. Scharff (1981) ArticleTitleCalmodulin and its role in cellular activation. Cell Calcium 2 1–27 Occurrence Handle1:CAS:528:DyaL3MXhsFWqurk%3D

    CAS  Google Scholar 

  26. O. Scharff B. Foder (1982) ArticleTitleRate constants for calmodulin binding to Ca2+-ATPase in erythrocyte membranes. Biochem. Biophys. Acta 691 133–143 Occurrence Handle1:CAS:528:DyaL38XlslOltr8%3D Occurrence Handle6215944

    CAS  PubMed  Google Scholar 

  27. B. Vestergaard-Bogind P. Bennekou (1982) ArticleTitleCalcium-induced oscillations in K+ conductance and membrane potential of human erythrocytes mediated by the ionophore A23187. Biochim. Biophys. Acta 688 37–44 Occurrence Handle1:CAS:528:DyaL38XitFGju7c%3D Occurrence Handle6284234

    CAS  PubMed  Google Scholar 

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Acknowledgements

Kirsten Abel, Gurli Bengtson and Søren L. Johansen are gratefully acknowledged for their expert assistance.

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Authors and Affiliations

  1. The August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100 Copenhagen, Denmark

    P. Bennekou & B. I. Kristensen

  2. NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark

    P. Christophersen

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  1. P. Bennekou
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  2. B. I. Kristensen
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  3. P. Christophersen
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Correspondence to P. Bennekou.

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Bennekou, P., Kristensen, B. & Christophersen, P. The Human Red Cell Voltage-regulated Cation Channel. The Interplay with the Chloride Conductance, the Ca2+-activated K+ Channel and the Ca2+ Pump . J. Membrane Biol. 195, 1–8 (2003). https://doi.org/10.1007/s00232-003-2036-6

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  • DOI: https://doi.org/10.1007/s00232-003-2036-6

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