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. 2002 Jun;82(6):3012–3021. doi: 10.1016/S0006-3495(02)75642-7

Ca(2+) influx and opening of Ca(2+)-activated K(+) channels in muscle fibers from control and mdx mice.

Nora Mallouk 1, Bruno Allard 1
PMCID: PMC1302089  PMID: 12023224

Abstract

Using the patch-clamp technique, we demonstrate that, in depolarized cell-attached patches from mouse skeletal muscle fibers, a short hyperpolarization to resting value is followed by a transient activation of Ca(2+)-activated K(+) channels (K(Ca)) upon return to depolarized levels. These results indicate that sparse sites of passive Ca(2+) influx at resting potentials are responsible for a subsarcolemmal Ca(2+) load high enough to induce K(Ca) channel activation upon muscle activation. We then investigate this phenomenon in mdx dystrophin-deficient muscle fibers, in which an elevated Ca(2+) influx and a subsequent subsarcolemmal Ca(2+) overload are suspected. The number of Ca(2+) entry sites detected with K(Ca) was found to be greater in mdx muscle. K(Ca) activity reflecting subsarcolemmal Ca(2+) load was also found to be independent of the activity of leak channels carrying inward currents at negative potentials in mdx muscle. These results indicate that the sites of passive Ca(2+) influx newly described in this study could represent the Ca(2+) influx pathways responsible for the subsarcolemmal Ca(2+) overload in mdx muscle fibers.

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Selected References

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  1. Allard B., Bernengo J. C., Rougier O., Jacquemond V. Intracellular Ca2+ changes and Ca2+-activated K+ channel activation induced by acetylcholine at the endplate of mouse skeletal muscle fibres. J Physiol. 1996 Jul 15;494(Pt 2):337–349. doi: 10.1113/jphysiol.1996.sp021496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bian S., Favre I., Moczydlowski E. Ca2+-binding activity of a COOH-terminal fragment of the Drosophila BK channel involved in Ca2+-dependent activation. Proc Natl Acad Sci U S A. 2001 Mar 27;98(8):4776–4781. doi: 10.1073/pnas.081072398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brum G., Rios E. Intramembrane charge movement in frog skeletal muscle fibres. Properties of charge 2. J Physiol. 1987 Jun;387:489–517. doi: 10.1113/jphysiol.1987.sp016586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Butler A., Tsunoda S., McCobb D. P., Wei A., Salkoff L. mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels. Science. 1993 Jul 9;261(5118):221–224. doi: 10.1126/science.7687074. [DOI] [PubMed] [Google Scholar]
  5. Cannell M. B., Sage S. O. Bradykinin-evoked changes in cytosolic calcium and membrane currents in cultured bovine pulmonary artery endothelial cells. J Physiol. 1989 Dec;419:555–568. doi: 10.1113/jphysiol.1989.sp017886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carter T. D., Ogden D. Kinetics of Ca2+ release by InsP3 in pig single aortic endothelial cells: evidence for an inhibitory role of cytosolic Ca2+ in regulating hormonally evoked Ca2+ spikes. J Physiol. 1997 Oct 1;504(Pt 1):17–33. doi: 10.1111/j.1469-7793.1997.00017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DiMario J. X., Uzman A., Strohman R. C. Fiber regeneration is not persistent in dystrophic (MDX) mouse skeletal muscle. Dev Biol. 1991 Nov;148(1):314–321. doi: 10.1016/0012-1606(91)90340-9. [DOI] [PubMed] [Google Scholar]
  8. Fahlke C., Rüdel R. Chloride currents across the membrane of mammalian skeletal muscle fibres. J Physiol. 1995 Apr 15;484(Pt 2):355–368. doi: 10.1113/jphysiol.1995.sp020670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Franco-Obregón A., Jr, Lansman J. B. Mechanosensitive ion channels in skeletal muscle from normal and dystrophic mice. J Physiol. 1994 Dec 1;481(Pt 2):299–309. doi: 10.1113/jphysiol.1994.sp020440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ganitkevich V. Y., Isenberg G. Dissociation of subsarcolemmal from global cytosolic [Ca2+] in myocytes from guinea-pig coronary artery. J Physiol. 1996 Jan 15;490(Pt 2):305–318. doi: 10.1113/jphysiol.1996.sp021145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gillis J. M. Understanding dystrophinopathies: an inventory of the structural and functional consequences of the absence of dystrophin in muscles of the mdx mouse. J Muscle Res Cell Motil. 1999 Oct;20(7):605–625. doi: 10.1023/a:1005545325254. [DOI] [PubMed] [Google Scholar]
  12. Gonzalez-Serratos H., Hilgemann D. W., Rozycka M., Gauthier A., Rasgado-Flores H. Na-Ca exchange studies in sarcolemmal skeletal muscle. Ann N Y Acad Sci. 1996 Apr 15;779:556–560. doi: 10.1111/j.1749-6632.1996.tb44837.x. [DOI] [PubMed] [Google Scholar]
  13. Guerini D., Garcia-Martin E., Zecca A., Guidi F., Carafoli E. The calcium pump of the plasma membrane: membrane targeting, calcium binding sites, tissue-specific isoform expression. Acta Physiol Scand Suppl. 1998 Aug;643:265–273. [PubMed] [Google Scholar]
  14. Haws C. M., Lansman J. B. Developmental regulation of mechanosensitive calcium channels in skeletal muscle from normal and mdx mice. Proc Biol Sci. 1991 Sep 23;245(1314):173–177. doi: 10.1098/rspb.1991.0105. [DOI] [PubMed] [Google Scholar]
  15. Hocherman S. D., Bezanilla F. A patch-clamp study of delayed rectifier currents in skeletal muscle of control and mdx mice. J Physiol. 1996 May 15;493(Pt 1):113–128. doi: 10.1113/jphysiol.1996.sp021368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hoffman E. P., Brown R. H., Jr, Kunkel L. M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987 Dec 24;51(6):919–928. doi: 10.1016/0092-8674(87)90579-4. [DOI] [PubMed] [Google Scholar]
  17. Hopf F. W., Turner P. R., Denetclaw W. F., Jr, Reddy P., Steinhardt R. A. A critical evaluation of resting intracellular free calcium regulation in dystrophic mdx muscle. Am J Physiol. 1996 Oct;271(4 Pt 1):C1325–C1339. doi: 10.1152/ajpcell.1996.271.4.C1325. [DOI] [PubMed] [Google Scholar]
  18. Jacquemond V., Allard B. Activation of Ca2+-activated K+ channels by an increase in intracellular Ca2+ induced by depolarization of mouse skeletal muscle fibres. J Physiol. 1998 May 15;509(Pt 1):93–102. doi: 10.1111/j.1469-7793.1998.093bo.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kaczorowski G. J., Knaus H. G., Leonard R. J., McManus O. B., Garcia M. L. High-conductance calcium-activated potassium channels; structure, pharmacology, and function. J Bioenerg Biomembr. 1996 Jun;28(3):255–267. doi: 10.1007/BF02110699. [DOI] [PubMed] [Google Scholar]
  20. Latorre R., Oberhauser A., Labarca P., Alvarez O. Varieties of calcium-activated potassium channels. Annu Rev Physiol. 1989;51:385–399. doi: 10.1146/annurev.ph.51.030189.002125. [DOI] [PubMed] [Google Scholar]
  21. Lännergren J., Westerblad H. Action potential fatigue in single skeletal muscle fibres of Xenopus. Acta Physiol Scand. 1987 Mar;129(3):311–318. doi: 10.1111/j.1748-1716.1987.tb08074.x. [DOI] [PubMed] [Google Scholar]
  22. Mallouk N., Allard B. Stretch-induced activation of Ca(2+)-activated K(+) channels in mouse skeletal muscle fibers. Am J Physiol Cell Physiol. 2000 Mar;278(3):C473–C479. doi: 10.1152/ajpcell.2000.278.3.C473. [DOI] [PubMed] [Google Scholar]
  23. Mallouk N., Jacquemond V., Allard B. Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K+ channels. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4950–4955. doi: 10.1073/pnas.97.9.4950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marrion N. V., Tavalin S. J. Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature. 1998 Oct 29;395(6705):900–905. doi: 10.1038/27674. [DOI] [PubMed] [Google Scholar]
  25. McDonald T. F., Pelzer S., Trautwein W., Pelzer D. J. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol Rev. 1994 Apr;74(2):365–507. doi: 10.1152/physrev.1994.74.2.365. [DOI] [PubMed] [Google Scholar]
  26. McManus O. B. Calcium-activated potassium channels: regulation by calcium. J Bioenerg Biomembr. 1991 Aug;23(4):537–560. doi: 10.1007/BF00785810. [DOI] [PubMed] [Google Scholar]
  27. Melzer W., Herrmann-Frank A., Lüttgau H. C. The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres. Biochim Biophys Acta. 1995 May 8;1241(1):59–116. doi: 10.1016/0304-4157(94)00014-5. [DOI] [PubMed] [Google Scholar]
  28. Menke A., Jockusch H. Decreased osmotic stability of dystrophin-less muscle cells from the mdx mouse. Nature. 1991 Jan 3;349(6304):69–71. doi: 10.1038/349069a0. [DOI] [PubMed] [Google Scholar]
  29. Parekh A. B., Penner R. Store depletion and calcium influx. Physiol Rev. 1997 Oct;77(4):901–930. doi: 10.1152/physrev.1997.77.4.901. [DOI] [PubMed] [Google Scholar]
  30. Penniston J. T., Enyedi A. Modulation of the plasma membrane Ca2+ pump. J Membr Biol. 1998 Sep 15;165(2):101–109. doi: 10.1007/s002329900424. [DOI] [PubMed] [Google Scholar]
  31. Rasmussen H., Barrett P. Q. Calcium messenger system: an integrated view. Physiol Rev. 1984 Jul;64(3):938–984. doi: 10.1152/physrev.1984.64.3.938. [DOI] [PubMed] [Google Scholar]
  32. Rios E., Brum G. Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle. Nature. 1987 Feb 19;325(6106):717–720. doi: 10.1038/325717a0. [DOI] [PubMed] [Google Scholar]
  33. Ríos E., Pizarro G. Voltage sensor of excitation-contraction coupling in skeletal muscle. Physiol Rev. 1991 Jul;71(3):849–908. doi: 10.1152/physrev.1991.71.3.849. [DOI] [PubMed] [Google Scholar]
  34. Spray T. L., Waugh R. A., Sommer J. R. Peripheral couplings in adult vertebrate skeletal muscle. Anatomical observations and functional implications. J Cell Biol. 1974 Jul;62(1):223–227. doi: 10.1083/jcb.62.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tang J. M., Wang J., Quandt F. N., Eisenberg R. S. Perfusing pipettes. Pflugers Arch. 1990 May;416(3):347–350. doi: 10.1007/BF00392072. [DOI] [PubMed] [Google Scholar]
  36. Turner P. R., Fong P. Y., Denetclaw W. F., Steinhardt R. A. Increased calcium influx in dystrophic muscle. J Cell Biol. 1991 Dec;115(6):1701–1712. doi: 10.1083/jcb.115.6.1701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tutdibi O., Brinkmeier H., Rüdel R., Föhr K. J. Increased calcium entry into dystrophin-deficient muscle fibres of MDX and ADR-MDX mice is reduced by ion channel blockers. J Physiol. 1999 Mar 15;515(Pt 3):859–868. doi: 10.1111/j.1469-7793.1999.859ab.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vergara C., Latorre R., Marrion N. V., Adelman J. P. Calcium-activated potassium channels. Curr Opin Neurobiol. 1998 Jun;8(3):321–329. doi: 10.1016/s0959-4388(98)80056-1. [DOI] [PubMed] [Google Scholar]
  39. Westerblad H., Allen D. G. Changes of myoplasmic calcium concentration during fatigue in single mouse muscle fibers. J Gen Physiol. 1991 Sep;98(3):615–635. doi: 10.1085/jgp.98.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]

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