Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 2000 Apr;78(4):1947–1954. doi: 10.1016/S0006-3495(00)76742-7

L-Type Ca(2+) channel charge movement and intracellular Ca(2+) in skeletal muscle fibers from aging mice.

Z M Wang 1, M L Messi 1, O Delbono 1
PMCID: PMC1300787  PMID: 10733973

Abstract

In this work we tested the hypothesis that skeletal muscle fibers from aging mice exhibit a significant decline in myoplasmic Ca(2+) concentration resulting from a reduction in L-type Ca(2+) channel (dihydropyridine receptor, DHPR) charge movement. Skeletal muscle fibers from the flexor digitorum brevis (FDB) muscle were obtained from 5-7-, 14-18-, or 21-24-month-old FVB mice and voltage-clamped in the whole-cell configuration of the patch-clamp technique according to described procedures (Wang, Z.-M., M. L. Messi, and O. Delbono. 1999. Biophys. J. 77:2709-2716). Total charge movement or the DHPR charge movement was measured simultaneously with intracellular Ca(2+) concentration. The maximum charge movement (Q(max)) recorded (mean +/- SEM, in nC microF(-1)) was 53 +/- 3.2 (n = 47), 51 +/- 3.2 (n = 35) (non-significant, ns), and 33 +/- 1.9 (n = 32) (p < 0.01), for the three age groups, respectively. Q(max) corresponding to the DHPR was 43 +/- 3.3, 38 +/- 4.1 (ns), and 25 +/- 3.4 (p < 0.01) for the three age groups, respectively. The peak intracellular [Ca(2+)] recorded at 40 mV (in microM) was 15.7 +/- 0. 12, 16.7 +/- 0.18 (ns), and 8.2 +/- 0.07 (p < 0.01) for the three age groups, respectively. No significant changes in the voltage distribution or steepness of the Q-V or [Ca(2+)]-V relationship were found. These data support the concept that the reduction in the peak intracellular [Ca(2+)] results from a larger number of ryanodine receptors uncoupled to DHPRs in skeletal muscle fibers from aging mammals.

Full Text

The Full Text of this article is available as a PDF (93.8 KB).

Selected References

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

  1. Adams B. A., Tanabe T., Mikami A., Numa S., Beam K. G. Intramembrane charge movement restored in dysgenic skeletal muscle by injection of dihydropyridine receptor cDNAs. Nature. 1990 Aug 9;346(6284):569–572. doi: 10.1038/346569a0. [DOI] [PubMed] [Google Scholar]
  2. Ashley C. C., Mulligan I. P., Lea T. J. Ca2+ and activation mechanisms in skeletal muscle. Q Rev Biophys. 1991 Feb;24(1):1–73. doi: 10.1017/s0033583500003267. [DOI] [PubMed] [Google Scholar]
  3. Beam K. G., Franzini-Armstrong C. Functional and structural approaches to the study of excitation-contraction coupling. Methods Cell Biol. 1997;52:283–306. doi: 10.1016/s0091-679x(08)60384-2. [DOI] [PubMed] [Google Scholar]
  4. Beuckelmann D. J., Wier W. G. Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. J Physiol. 1988 Nov;405:233–255. doi: 10.1113/jphysiol.1988.sp017331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bezanilla F. Gating of sodium and potassium channels. J Membr Biol. 1985;88(2):97–111. doi: 10.1007/BF01868424. [DOI] [PubMed] [Google Scholar]
  6. Booth F. W., Weeden S. H., Tseng B. S. Effect of aging on human skeletal muscle and motor function. Med Sci Sports Exerc. 1994 May;26(5):556–560. [PubMed] [Google Scholar]
  7. Brooks S. V., Faulkner J. A. Contractile properties of skeletal muscles from young, adult and aged mice. J Physiol. 1988 Oct;404:71–82. doi: 10.1113/jphysiol.1988.sp017279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brooks S. V., Faulkner J. A. Isometric, shortening, and lengthening contractions of muscle fiber segments from adult and old mice. Am J Physiol. 1994 Aug;267(2 Pt 1):C507–C513. doi: 10.1152/ajpcell.1994.267.2.C507. [DOI] [PubMed] [Google Scholar]
  9. Brooks S. V., Faulkner J. A. Skeletal muscle weakness in old age: underlying mechanisms. Med Sci Sports Exerc. 1994 Apr;26(4):432–439. [PubMed] [Google Scholar]
  10. Delbono O. Calcium current activation and charge movement in denervated mammalian skeletal muscle fibres. J Physiol. 1992;451:187–203. doi: 10.1113/jphysiol.1992.sp019160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Delbono O., Meissner G. Sarcoplasmic reticulum Ca2+ release in rat slow- and fast-twitch muscles. J Membr Biol. 1996 May;151(2):123–130. doi: 10.1007/s002329900063. [DOI] [PubMed] [Google Scholar]
  12. Delbono O., O'Rourke K. S., Ettinger W. H. Excitation-calcium release uncoupling in aged single human skeletal muscle fibers. J Membr Biol. 1995 Dec;148(3):211–222. doi: 10.1007/BF00235039. [DOI] [PubMed] [Google Scholar]
  13. Delbono O., Renganathan M., Messi M. L. Excitation-Ca2+ release-contraction coupling in single aged human skeletal muscle fiber. Muscle Nerve Suppl. 1997;5:S88–S92. doi: 10.1002/(sici)1097-4598(1997)5+<88::aid-mus21>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  14. Delbono O., Renganathan M., Messi M. L. Regulation of mouse skeletal muscle L-type Ca2+ channel by activation of the insulin-like growth factor-1 receptor. J Neurosci. 1997 Sep 15;17(18):6918–6928. doi: 10.1523/JNEUROSCI.17-18-06918.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Delbono O., Stefani E. Calcium current inactivation in denervated rat skeletal muscle fibres. J Physiol. 1993 Jan;460:173–183. doi: 10.1113/jphysiol.1993.sp019465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Delbono O., Stefani E. Calcium transients in single mammalian skeletal muscle fibres. J Physiol. 1993 Apr;463:689–707. doi: 10.1113/jphysiol.1993.sp019617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Eddinger T. J., Moss R. L., Cassens R. G. Fiber number and type composition in extensor digitorum longus, soleus, and diaphragm muscles with aging in Fisher 344 rats. J Histochem Cytochem. 1985 Oct;33(10):1033–1041. doi: 10.1177/33.10.2931475. [DOI] [PubMed] [Google Scholar]
  18. Edström L., Larsson L. Effects of age on contractile and enzyme-histochemical properties of fast- and slow-twitch single motor units in the rat. J Physiol. 1987 Nov;392:129–145. doi: 10.1113/jphysiol.1987.sp016773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fabiato A. Computer programs for calculating total from specified free or free from specified total ionic concentrations in aqueous solutions containing multiple metals and ligands. Methods Enzymol. 1988;157:378–417. doi: 10.1016/0076-6879(88)57093-3. [DOI] [PubMed] [Google Scholar]
  20. Finch E. A., Augustine G. J. Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites. Nature. 1998 Dec 24;396(6713):753–756. doi: 10.1038/25541. [DOI] [PubMed] [Google Scholar]
  21. Garcia J., Schneider M. F. Calcium transients and calcium release in rat fast-twitch skeletal muscle fibres. J Physiol. 1993 Apr;463:709–728. doi: 10.1113/jphysiol.1993.sp019618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  23. Klein M. G., Cheng H., Santana L. F., Jiang Y. H., Lederer W. J., Schneider M. F. Two mechanisms of quantized calcium release in skeletal muscle. Nature. 1996 Feb 1;379(6564):455–458. doi: 10.1038/379455a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Moore D. H., 2nd A study of age group track and field records to relate age and running speed. Nature. 1975 Jan 24;253(5489):264–265. doi: 10.1038/253264a0. [DOI] [PubMed] [Google Scholar]
  26. Niggli E. Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks. Annu Rev Physiol. 1999;61:311–335. doi: 10.1146/annurev.physiol.61.1.311. [DOI] [PubMed] [Google Scholar]
  27. Renganathan M., Messi M. L., Delbono O. Dihydropyridine receptor-ryanodine receptor uncoupling in aged skeletal muscle. J Membr Biol. 1997 Jun 1;157(3):247–253. doi: 10.1007/s002329900233. [DOI] [PubMed] [Google Scholar]
  28. Renganathan M., Messi M. L., Delbono O. Overexpression of IGF-1 exclusively in skeletal muscle prevents age-related decline in the number of dihydropyridine receptors. J Biol Chem. 1998 Oct 30;273(44):28845–28851. doi: 10.1074/jbc.273.44.28845. [DOI] [PubMed] [Google Scholar]
  29. Shirokova N., García J., Pizarro G., Ríos E. Ca2+ release from the sarcoplasmic reticulum compared in amphibian and mammalian skeletal muscle. J Gen Physiol. 1996 Jan;107(1):1–18. doi: 10.1085/jgp.107.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shirokova N., García J., Ríos E. Local calcium release in mammalian skeletal muscle. J Physiol. 1998 Oct 15;512(Pt 2):377–384. doi: 10.1111/j.1469-7793.1998.377be.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tsugorka A., Ríos E., Blatter L. A. Imaging elementary events of calcium release in skeletal muscle cells. Science. 1995 Sep 22;269(5231):1723–1726. doi: 10.1126/science.7569901. [DOI] [PubMed] [Google Scholar]
  32. Wang Z. M., Messi M. L., Delbono O. Patch-clamp recording of charge movement, Ca2+ current, and Ca2+ transients in adult skeletal muscle fibers. Biophys J. 1999 Nov;77(5):2709–2716. doi: 10.1016/s0006-3495(99)77104-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wang Z. M., Messi M. L., Renganathan M., Delbono O. Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L-type Ca2+ channel gene expression. J Physiol. 1999 Apr 15;516(Pt 2):331–341. doi: 10.1111/j.1469-7793.1999.0331v.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES