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. 1996 May 15;316(Pt 1):19–23. doi: 10.1042/bj3160019

Differential distribution of ryanodine receptor type 3 (RyR3) gene product in mammalian skeletal muscles.

A Conti 1, L Gorza 1, V Sorrentino 1
PMCID: PMC1217321  PMID: 8645204

Abstract

Activation of intracellular Ca(2+)-release channels/ryanodine receptors (RyRs) is a fundamental step in the regulation of muscle contraction. In mammalian skeletal muscle, Ca(2+)-release channels containing the type 1 isoform of RyR (RyR1) open to release Ca2+ from the sarcoplasmic reticulum (SR) upon stimulation by the voltage-activated dihydropyridine receptor on the T-tubule/plasma membrane. In addition to RyR1, low levels of the mRNA of the RyR3 isoform have been recently detected in mammalian skeletal muscles. Here we report data on the distribution of the RyR3 gene product in mammalian skeletal muscles. Western-blot analysis of SR of individual muscles indicated that, at variance with the even distribution of the RyR1 isoform, the RyR3 content varies among different muscles, with relatively higher amounts being detected in diaphragm and soleus, and lower levels in abdominal muscles and tibialis anterior. In these muscles RyR3 was localized in the terminal cisternae of the SR. No detectable levels of RyR3 were observed in the extensor digitorum longus. Preferential high content of RyR3 in the diaphragm muscle was observed in several mammalian species. In situ hybridization analysis demonstrated that RyR3 transcripts are not restricted to a specific subset of skeletal-muscle fibres. Differential utilization of the RyR3 isoform in skeletal muscle may be relevant to the modulation of Ca2+ release with respect to specific muscle-contraction properties.

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Selected References

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

  1. Airey J. A., Grinsell M. M., Jones L. R., Sutko J. L., Witcher D. Three ryanodine receptor isoforms exist in avian striated muscles. Biochemistry. 1993 Jun 8;32(22):5739–5745. doi: 10.1021/bi00073a003. [DOI] [PubMed] [Google Scholar]
  2. Anderson K., Cohn A. H., Meissner G. High-affinity [3H]PN200-110 and [3H]ryanodine binding to rabbit and frog skeletal muscle. Am J Physiol. 1994 Feb;266(2 Pt 1):C462–C466. doi: 10.1152/ajpcell.1994.266.2.C462. [DOI] [PubMed] [Google Scholar]
  3. Arai M., Otsu K., MacLennan D. H., Periasamy M. Regulation of sarcoplasmic reticulum gene expression during cardiac and skeletal muscle development. Am J Physiol. 1992 Mar;262(3 Pt 1):C614–C620. doi: 10.1152/ajpcell.1992.262.3.C614. [DOI] [PubMed] [Google Scholar]
  4. Bers D. M., Stiffel V. M. Ratio of ryanodine to dihydropyridine receptors in cardiac and skeletal muscle and implications for E-C coupling. Am J Physiol. 1993 Jun;264(6 Pt 1):C1587–C1593. doi: 10.1152/ajpcell.1993.264.6.C1587. [DOI] [PubMed] [Google Scholar]
  5. Biral D., Damiani E., Volpe P., Salviati G., Margreth A. Polymorphism of myosin light chains. An electrophoretic and immunological study of rabbit skeletal-muscle myosins. Biochem J. 1982 Jun 1;203(3):529–540. doi: 10.1042/bj2030529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Block B. A., Imagawa T., Campbell K. P., Franzini-Armstrong C. Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. J Cell Biol. 1988 Dec;107(6 Pt 2):2587–2600. doi: 10.1083/jcb.107.6.2587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bull R., Marengo J. J. Sarcoplasmic reticulum release channels from frog skeletal muscle display two types of calcium dependence. FEBS Lett. 1993 Oct 4;331(3):223–227. doi: 10.1016/0014-5793(93)80341-q. [DOI] [PubMed] [Google Scholar]
  8. Colyer J., Mata A. M., Lee A. G., East J. M. Effects on ATPase activity of monoclonal antibodies raised against (Ca2+ + Mg2+)-ATPase from rabbit skeletal muscle sarcoplasmic reticulum and their correlation with epitope location. Biochem J. 1989 Sep 1;262(2):439–447. doi: 10.1042/bj2620439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Damiani E., Margreth A. Characterization study of the ryanodine receptor and of calsequestrin isoforms of mammalian skeletal muscles in relation to fibre types. J Muscle Res Cell Motil. 1994 Apr;15(2):86–101. doi: 10.1007/BF00130421. [DOI] [PubMed] [Google Scholar]
  10. DeNardi C., Ausoni S., Moretti P., Gorza L., Velleca M., Buckingham M., Schiaffino S. Type 2X-myosin heavy chain is coded by a muscle fiber type-specific and developmentally regulated gene. J Cell Biol. 1993 Nov;123(4):823–835. doi: 10.1083/jcb.123.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fleischer S., Inui M. Biochemistry and biophysics of excitation-contraction coupling. Annu Rev Biophys Biophys Chem. 1989;18:333–364. doi: 10.1146/annurev.bb.18.060189.002001. [DOI] [PubMed] [Google Scholar]
  12. Franzini-Armstrong C., Jorgensen A. O. Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol. 1994;56:509–534. doi: 10.1146/annurev.ph.56.030194.002453. [DOI] [PubMed] [Google Scholar]
  13. Franzini-Armstrong C., Kish J. W. Alternate disposition of tetrads in peripheral couplings of skeletal muscle. J Muscle Res Cell Motil. 1995 Jun;16(3):319–324. doi: 10.1007/BF00121140. [DOI] [PubMed] [Google Scholar]
  14. Gauthier G. F., Lowey S., Benfield P. A., Hobbs A. W. Distribution and properties of myosin isozymes in developing avian and mammalian skeletal muscle fibers. J Cell Biol. 1982 Feb;92(2):471–484. doi: 10.1083/jcb.92.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Giannini G., Clementi E., Ceci R., Marziali G., Sorrentino V. Expression of a ryanodine receptor-Ca2+ channel that is regulated by TGF-beta. Science. 1992 Jul 3;257(5066):91–94. doi: 10.1126/science.1320290. [DOI] [PubMed] [Google Scholar]
  16. Giannini G., Conti A., Mammarella S., Scrobogna M., Sorrentino V. The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. J Cell Biol. 1995 Mar;128(5):893–904. doi: 10.1083/jcb.128.5.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. González A., Ríos E. Perchlorate enhances transmission in skeletal muscle excitation-contraction coupling. J Gen Physiol. 1993 Sep;102(3):373–421. doi: 10.1085/jgp.102.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gorza L. Identification of a novel type 2 fiber population in mammalian skeletal muscle by combined use of histochemical myosin ATPase and anti-myosin monoclonal antibodies. J Histochem Cytochem. 1990 Feb;38(2):257–265. doi: 10.1177/38.2.2137154. [DOI] [PubMed] [Google Scholar]
  19. Gorza L., Schiaffino S., Volpe P. Inositol 1,4,5-trisphosphate receptor in heart: evidence for its concentration in Purkinje myocytes of the conduction system. J Cell Biol. 1993 Apr;121(2):345–353. doi: 10.1083/jcb.121.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Inui M., Saito A., Fleischer S. Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem. 1987 Feb 5;262(4):1740–1747. [PubMed] [Google Scholar]
  21. Ivanenko A., McKemy D. D., Kenyon J. L., Airey J. A., Sutko J. L. Embryonic chicken skeletal muscle cells fail to develop normal excitation-contraction coupling in the absence of the alpha ryanodine receptor. Implications for a two-ryanodine receptor system. J Biol Chem. 1995 Mar 3;270(9):4220–4223. doi: 10.1074/jbc.270.9.4220. [DOI] [PubMed] [Google Scholar]
  22. Jacquemond V., Csernoch L., Klein M. G., Schneider M. F. Voltage-gated and calcium-gated calcium release during depolarization of skeletal muscle fibers. Biophys J. 1991 Oct;60(4):867–873. doi: 10.1016/S0006-3495(91)82120-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kushmerick M. J., Moerland T. S., Wiseman R. W. Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7521–7525. doi: 10.1073/pnas.89.16.7521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lai F. A., Erickson H. P., Rousseau E., Liu Q. Y., Meissner G. Purification and reconstitution of the calcium release channel from skeletal muscle. Nature. 1988 Jan 28;331(6154):315–319. doi: 10.1038/331315a0. [DOI] [PubMed] [Google Scholar]
  25. Lamb G. D. DHP receptors and excitation-contraction coupling. J Muscle Res Cell Motil. 1992 Aug;13(4):394–405. doi: 10.1007/BF01738035. [DOI] [PubMed] [Google Scholar]
  26. Lamb G. D., Walsh T. Calcium currents, charge movement and dihydropyridine binding in fast- and slow-twitch muscles of rat and rabbit. J Physiol. 1987 Dec;393:595–617. doi: 10.1113/jphysiol.1987.sp016843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lu X., Xu L., Meissner G. Activation of the skeletal muscle calcium release channel by a cytoplasmic loop of the dihydropyridine receptor. J Biol Chem. 1994 Mar 4;269(9):6511–6516. [PubMed] [Google Scholar]
  28. Ma J., Anderson K., Shirokov R., Levis R., González A., Karhanek M., Hosey M. M., Meissner G., Ríos E. Effects of perchlorate on the molecules of excitation-contraction coupling of skeletal and cardiac muscle. J Gen Physiol. 1993 Sep;102(3):423–448. doi: 10.1085/jgp.102.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Marty I., Robert M., Villaz M., De Jongh K., Lai Y., Catterall W. A., Ronjat M. Biochemical evidence for a complex involving dihydropyridine receptor and ryanodine receptor in triad junctions of skeletal muscle. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2270–2274. doi: 10.1073/pnas.91.6.2270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mattei M. G., Giannini G., Moscatelli F., Sorrentino V. Chromosomal localization of murine ryanodine receptor genes RYR1, RYR2, and RYR3 by in situ hybridization. Genomics. 1994 Jul 1;22(1):202–204. doi: 10.1006/geno.1994.1362. [DOI] [PubMed] [Google Scholar]
  31. Meissner G. Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. Annu Rev Physiol. 1994;56:485–508. doi: 10.1146/annurev.ph.56.030194.002413. [DOI] [PubMed] [Google Scholar]
  32. Moschella M. C., Watras J., Jayaraman T., Marks A. R. Inositol 1,4,5-trisphosphate receptor in skeletal muscle: differential expression in myofibres. J Muscle Res Cell Motil. 1995 Aug;16(4):390–400. doi: 10.1007/BF00114504. [DOI] [PubMed] [Google Scholar]
  33. O'Brien J., Meissner G., Block B. A. The fastest contracting muscles of nonmammalian vertebrates express only one isoform of the ryanodine receptor. Biophys J. 1993 Dec;65(6):2418–2427. doi: 10.1016/S0006-3495(93)81303-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. O'Brien J., Valdivia H. H., Block B. A. Physiological differences between the alpha and beta ryanodine receptors of fish skeletal muscle. Biophys J. 1995 Feb;68(2):471–482. doi: 10.1016/S0006-3495(95)80208-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Olivares E. B., Tanksley S. J., Airey J. A., Beck C. F., Ouyang Y., Deerinck T. J., Ellisman M. H., Sutko J. L. Nonmammalian vertebrate skeletal muscles express two triad junctional foot protein isoforms. Biophys J. 1991 Jun;59(6):1153–1163. doi: 10.1016/S0006-3495(91)82331-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ottini L., Marziali G., Conti A., Charlesworth A., Sorrentino V. Alpha and beta isoforms of ryanodine receptor from chicken skeletal muscle are the homologues of mammalian RyR1 and RyR3. Biochem J. 1996 Apr 1;315(Pt 1):207–216. doi: 10.1042/bj3150207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Oyamada H., Murayama T., Takagi T., Iino M., Iwabe N., Miyata T., Ogawa Y., Endo M. Primary structure and distribution of ryanodine-binding protein isoforms of the bullfrog skeletal muscle. J Biol Chem. 1994 Jun 24;269(25):17206–17214. [PubMed] [Google Scholar]
  38. Percival A. L., Williams A. J., Kenyon J. L., Grinsell M. M., Airey J. A., Sutko J. L. Chicken skeletal muscle ryanodine receptor isoforms: ion channel properties. Biophys J. 1994 Nov;67(5):1834–1850. doi: 10.1016/S0006-3495(94)80665-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pette D., Staron R. S. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol Biochem Pharmacol. 1990;116:1–76. doi: 10.1007/3540528806_3. [DOI] [PubMed] [Google Scholar]
  40. Ríos E., Karhanek M., Ma J., González A. An allosteric model of the molecular interactions of excitation-contraction coupling in skeletal muscle. J Gen Physiol. 1993 Sep;102(3):449–481. doi: 10.1085/jgp.102.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ríos E., Pizarro G., Stefani E. Charge movement and the nature of signal transduction in skeletal muscle excitation-contraction coupling. Annu Rev Physiol. 1992;54:109–133. doi: 10.1146/annurev.ph.54.030192.000545. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Saito A., Seiler S., Chu A., Fleischer S. Preparation and morphology of sarcoplasmic reticulum terminal cisternae from rabbit skeletal muscle. J Cell Biol. 1984 Sep;99(3):875–885. doi: 10.1083/jcb.99.3.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schneider M. F. Control of calcium release in functioning skeletal muscle fibers. Annu Rev Physiol. 1994;56:463–484. doi: 10.1146/annurev.ph.56.030194.002335. [DOI] [PubMed] [Google Scholar]
  45. Sorrentino V., Volpe P. Ryanodine receptors: how many, where and why? Trends Pharmacol Sci. 1993 Mar;14(3):98–103. doi: 10.1016/0165-6147(93)90072-r. [DOI] [PubMed] [Google Scholar]
  46. Takeshima H., Iino M., Takekura H., Nishi M., Kuno J., Minowa O., Takano H., Noda T. Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene. Nature. 1994 Jun 16;369(6481):556–559. doi: 10.1038/369556a0. [DOI] [PubMed] [Google Scholar]
  47. Takeshima H., Yamazawa T., Ikemoto T., Takekura H., Nishi M., Noda T., Iino M. Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor. EMBO J. 1995 Jul 3;14(13):2999–3006. doi: 10.1002/j.1460-2075.1995.tb07302.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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