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Excitation-contraction coupling in skeletal muscle: recent progress and unanswered questions

Abstract

Excitation-contraction coupling (ECC) is a physiological process that links excitation of muscles by the nervous system to their mechanical contraction. In skeletal muscle, ECC is initiated with an action potential, generated by the somatic nervous system, which causes a depolarisation of the muscle fibre membrane (sarcolemma). This leads to a rapid change in the transmembrane potential, which is detected by the voltage-gated Ca2+ channel dihydropyridine receptor (DHPR) embedded in the sarcolemma. DHPR transmits the contractile signal to another Ca2+ channel, ryanodine receptor (RyR1), embedded in the membrane of the sarcoplasmic reticulum (SR), which releases a large amount of Ca2+ ions from the SR that initiate muscle contraction. Despite the fundamental role of ECC in skeletal muscle function of all vertebrate species, the molecular mechanism underpinning the communication between the two key proteins involved in the process (DHPR and RyR1) is still largely unknown. The goal of this work is to review the recent progress in our understanding of ECC in skeletal muscle from the point of view of the structure and interactions of proteins involved in the process, and to highlight the unanswered questions in the field.

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References

  1. Adams BA, Tanabe T, Mikami A, Numa S, Beam KG (1990) Intramembrane charge movement restored in dysgenic skeletal muscle by injection of dihydropyridine receptor cDNAs. Nature 346:569–572

  2. Ahern CA, Bhattacharya D, Mortenson L, Coronado R (2001) A component of excitation-contraction coupling triggered in the absence of the T671-L690 and L720-Q765 regions of the II-III loop of the dihydropyridine receptor α1s pore subunit. Biophys J 81:3294–3307

  3. Bannister RA (2007) Bridging the myoplasmic gap: recent developments in skeletal muscle excitation–contraction coupling. J Muscle Res Cell M 28:275–283

  4. Bannister RA (2016) Bridging the myoplasmic gap II: more recent advances in skeletal muscle excitation–contraction coupling. J Exp Biol 219:175–182

  5. Bannister RA, Beam KG (2005) The α1S N-terminus is not essential for bi-directional coupling with RyR1. Biochem Bioph Res Commun 336:134–141

  6. Bannister RA, Grabner M, Beam KG (2008) The α1S III-IV loop influences 1,4-dihydropyridine receptor gating but is not directly involved in excitation-contraction coupling interactions with the type 1 ryanodine receptor. J Biol Chem 283:23217–23223

  7. Bannister RA, Papadopoulos S, Haarmann CS, Beam KG (2009) Effects of inserting fluorescent proteins into the α1S II–III loop: insights into excitation–contraction coupling. J Gen Physiol 134:35–51

  8. Beam KG, Bannister RA (2010) Looking for answers to EC coupling’s persistent questions. J Gen Physiol 136:7–12

  9. Beurg M, Ahern CA, Vallejo P, Conklin MW, Powers PA, Gregg RG, Coronado R (1999) Involvement of the carboxy-terminus region of the dihydropyridine receptor β1a subunit in excitation-contraction coupling of skeletal muscle. Biophys J 77:2953–2967

  10. Block BA, Imagawa T, Campbell KP, Franzini-Armstrong C (1988) Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. J Cell Biol 107:2587–2600

  11. Bower NI, de la Serrana DG, Cole NJ, Hollway GE, Lee H-T, Assinder S, Johnston IA (2012) Stac3 is required for myotube formation and myogenic differentiation in vertebrate skeletal muscle. J Biol Chem 287:43936–43949

  12. Buraei Z, Yang J (2010) The β subunit of voltage-gated Ca2+ channels. Physiol Rev 90:1461–1506

  13. Calderón JC, Bolaños P, Caputo C (2014) The excitation–contraction coupling mechanism in skeletal muscle. Biophys Rev 6:133–160

  14. Campiglio M, de Bagneaux PC, Ortner NJ, Tuluc P, Van Petegem F, Flucher BE (2018a) STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-dependent inactivation. Proc Natl Acad Sci U S A 115:1376–1381

  15. Campiglio M, Flucher BE (2017) STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal muscle triads. Sci Rep 7:41003

  16. Campiglio M, Kaplan MM, Flucher BE (2018b) STAC3 incorporation into skeletal muscle triads occurs independent of the dihydropyridine receptor. J Cell Physiol 233:9045–9051

  17. Casarotto MG, Cui Y, Karunasekara Y, Harvey PJ, Norris N, Board PG, Dulhunty AF (2006) Structural and functional characterization of interactions between the dihydropyridine receptor II-III loop and the ryanodine receptor. Clin Exp Pharmacol Physiol 33:1114–1117

  18. Catterall WA (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol 3:a003947

  19. Chen Y-H, Li M-H, Zhang Y, He L-l, Yamada Y, Fitzmaurice A, Shen Y, Zhang H, Tong L, Yang J (2004) Structural basis of the α1–β subunit interaction of voltage-gated Ca2+ channels. Nature 429:675–680

  20. Cheng W, Altafaj X, Ronjat M, Coronado R (2005) Interaction between the dihydropyridine receptor Ca2+ channel β-subunit and ryanodine receptor type 1 strengthens excitation-contraction coupling. Proc Natl Acad Sci U S A 102:19225–19230

  21. Coronado R, Ahern CA, Sheridan DC, Cheng W, Carbonneau L, Bhattacharya D (2004) Functional equivalence of dihydropyridine receptor a1S and b1a subunits in triggering excitation-contraction coupling in skeletal muscle. Biol Res 37:565–575

  22. Cui Y, Tae H-S, Norris NC, Karunasekara Y, Pouliquin P, Board PG, Dulhunty AF, Casarotto MG (2009) A dihydropyridine receptor α1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor. Int J Biochem Cell Biol 41:677–686

  23. Dayal A, Bhat V, Franzini-Armstrong C, Grabner M (2013) Domain cooperativity in the β1a subunit is essential for dihydropyridine receptor voltage sensing in skeletal muscle. Proc Natl Acad Sci U S A 110:7488–7493

  24. Dayal A, Schredelseker J, Franzini-Armstrong C, Grabner M (2010) Skeletal muscle excitation–contraction coupling is independent of a conserved heptad repeat motif in the C-terminus of the DHPRβ1a subunit. Cell Calcium 47:500–506

  25. Dayal A, Schrötter K, Pan Y, Föhr K, Melzer W, Grabner M (2017) The Ca2+ influx through the mammalian skeletal muscle dihydropyridine receptor is irrelevant for muscle performance. Nat Commun 8:475

  26. Dirksen RT (2002) Bi-directional coupling between dihydropyridine receptors and ryanodine receptors. Front Biosci 7:d659–d670

  27. Dirksen RT, Beam KG (1999) Role of calcium permeation in dihydropyridine receptor function: insights into channel gating and excitation–contraction coupling. J Gen Physiol 114:393–404

  28. Dolphin AC (2003) β subunits of voltage-gated calcium channels. J Bioenerg Biomembr 35:599–620

  29. Dulhunty AF, Haarmann CS, Green D, Laver DR, Board PG, Casarotto MG (2002) Interactions between dihydropyridine receptors and ryanodine receptors in striated muscle. Prog Biophys Mol Biol 79:45–75

  30. Efremov RG, Leitner A, Aebersold R, Raunser S (2015) Architecture and conformational switch mechanism of the ryanodine receptor. Nature 517:39–43

  31. El-Hayek R, Antoniu B, Wang J, Hamilton SL, Ikemoto N (1995) Identification of calcium release-triggering and blocking regions of the II-III loop of the skeletal muscle dihydropyridine receptor. J Biol Chem 270:22116–22118

  32. El-Hayek R, Ikemoto N (1998) Identification of the minimum essential region in the II-III loop of the dihydropyridine receptor α1 subunit required for activation of skeletal muscle-type excitation-contraction coupling. Biochemistry 37:7015–7020

  33. Eltit JM, Franzini-Armstrong C, Perez CF (2014) Amino acid residues 489–503 of dihydropyridine receptor (DHPR) β1a subunit are critical for structural communication between the skeletal muscle DHPR complex and type 1 ryanodine receptor. J Biol Chem 289:36116–36124

  34. Flucher BE, Campiglio M (2018) STAC proteins: the missing link in skeletal muscle EC coupling and new regulators of calcium channel function. BBA-Mol Cell Res 1866:1101–1110

  35. Flucher BE, Kasielke N, Grabner M (2000) The triad targeting signal of the skeletal muscle calcium channel is localized in the COOH terminus of the α1S subunit. J Cell Biol 151:467–478

  36. Franzini-Armstrong C, Protasi F (1997) Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. Physiol Rev 77:699–729

  37. Ge X, Zhang Y, Park S, Cong X, Gerrard DE, Jiang H (2014) Stac3 inhibits myoblast differentiation into myotubes. PLoS One 9:e95926

  38. Golini L, Chouabe C, Berthier C, Cusimano V, Fornaro M, Bonvallet R, Formoso L, Giacomello E, Jacquemond V, Sorrentino V (2011) Junctophilin 1 and 2 proteins interact with the L-type Ca2+ channel dihydropyridine receptors (DHPRs) in skeletal muscle. J Biol Chem 286:43717–43725

  39. Grabner M, Dirksen RT, Suda N, Beam KG (1999) The II-III loop of the skeletal muscle dihydropyridine receptor is responsible for the bi-directional coupling with the ryanodine receptor. J Biol Chem 274:21913–21919

  40. Gregg RG, Messing A, Strube C, Beurg M, Moss R, Behan M, Sukhareva M, Haynes S, Powell JA, Coronado R, Powers PA (1996) Absence of the β subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the α1 subunit and eliminates excitation-contraction coupling. Proc Natl Acad Sci U S A 93:13961–13966

  41. Hernández-Ochoa EO, Olojo RO, Rebbeck RT, Dulhunty AF, Schneider MF (2014) β1a490–508, a 19-residue peptide from C-terminal tail of Cav1.1 β1a subunit, potentiates voltage-dependent calcium release in adult skeletal muscle fibers. Biophys J 106:535–547

  42. Horstick EJ, Linsley JW, Dowling JJ, Hauser MA, McDonald KK, Ashley-Koch A, Saint-Amant L, Satish A, Cui WW, Zhou W, Sprague SM, Stamm DS, Powell CM, Speer MC, Franzini-Armstrong C, Hirata H, Kuwada JY (2013) Stac3 is a component of the excitation–contraction coupling machinery and mutated in Native American myopathy. Nat Commun 4:1952

  43. Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F (2018) Congenital myopathies: disorders of excitation–contraction coupling and muscle contraction. Nat Rev Neurol 14:151–167

  44. Karunasekara Y, Dulhunty AF, Casarotto MG (2009) The voltage-gated calcium-channel β subunit: more than just an accessory. Eur Biophys J 39:75–81

  45. Karunasekara Y, Rebbeck RT, Weaver LM, Board PG, Dulhunty AF, Casarotto MG (2012) An α-helical C-terminal tail segment of the skeletal L-type Ca2+ channel β1a subunit activates ryanodine receptor type 1 via a hydrophobic surface. FASEB J 26:5049–5059

  46. Kugler G, Weiss RG, Flucher BE, Grabner M (2004) Structural requirements of the dihydropyridine receptor α1S II-III loop for skeletal-type excitation-contraction coupling. J Biol Chem 279:4721–4728

  47. Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2:a003996

  48. Linsley JW, Hsu I-U, Groom L, Yarotskyy V, Lavorato M, Horstick EJ, Linsley D, Wang W, Franzini-Armstrong C, Dirksen RT, Kuwada JY (2017) Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3. Proc Natl Acad Sci U S A 114:E228–E236

  49. Mayer BJ (2001) SH3 domains: complexity in moderation. J Cell Sci 114:1253–1263

  50. Meissner G, Lu X (1995) Dihydropyridine receptor-ryanodine receptor interactions in skeletal muscle excitation-contraction coupling. Biosci Rep 15:399–408

  51. Murphy RM, Dutka TL, Horvath D, Bell JR, Delbridge LM, Lamb GD (2013) Ca2+-dependent proteolysis of junctophilin-1 and junctophilin-2 in skeletal and cardiac muscle. J Physiol 591:719–729

  52. Nakada T, Kashihara T, Komatsu M, Kojima K, Takeshita T, Yamada M (2018) Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction. Proc Natl Acad Sci U S A 115:4507–4512

  53. Nakai J, Dirksen RT, Nguyen HT, Pessah IN, Beam KG, Allen PD (1996) Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor. Nature 380:72–75

  54. Nakai J, Ogura T, Protasi F, Franzini-Armstrong C, Allen PD, Beam KG (1997) Functional nonequality of the cardiac and skeletal ryanodine receptors. Proc Natl Acad Sci U S A 94:1019–1022

  55. Nakai J, Sekiguchi N, Rando TA, Allen PD, Beam KG (1998a) Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels. J Biol Chem 273:13403–13406

  56. Nakai J, Tanabe T, Konno T, Adams B, Beam KG (1998b) Localization in the II-III loop of the dihydropyridine receptor of a sequence critical for excitation-contraction coupling. J Biol Chem 273:24983–24986

  57. Nelson BR, Wu F, Liu Y, Anderson DM, McAnally J, Lin W, Cannon SC, Bassel-Duby R, Olson EN (2013) Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility. Proc Natl Acad Sci U S A 110:11881–11886

  58. Neuhuber B, Gerster U, Döring F, Glossmann H, Tanabe T, Flucher BE (1998) Association of calcium channel α1S and β1a subunits is required for the targeting of β1a but not of α1S into skeletal muscle triads. Proc Natl Acad Sci U S A 95:5015–5020

  59. Nishi M, Mizushima A, K-i N, Takeshima H (2000) Characterization of human junctophilin subtype genes. Biochem Bioph Res Commun 273:920–927

  60. Niu J, Dick IE, Yang W, Bamgboye MA, Yue DT, Tomaselli G, Inoue T, Ben-Johny M (2018a) Allosteric regulators selectively prevent Ca2+-feedback of CaV and NaV channels. eLife 7:e35222

  61. Niu J, Yang W, Yue DT, Inoue T, Ben-Johny M (2018b) Duplex signaling by CaM and Stac3 enhances CaV1.1 function and provides insights into congenital myopathy. J Gen Physiol 150:1145–1161

  62. Norris NC, Joseph S, Aditya S, Karunasekara Y, Board PG, Dulhunty AF, Oakley AJ, Casarotto MG (2017) Structural and biophysical analyses of the skeletal dihydropyridine receptor β subunit β1a reveal critical roles of domain interactions for stability. J Biol Chem 292:8401–8411

  63. Obermair GJ, Tuluc P, Flucher BE (2008) Auxiliary Ca2+ channel subunits: lessons learned from muscle. Curr Opin Pharmacol 8:311–318

  64. Opatowsky Y, Chen C-C, Campbell KP, Hirsch JA (2004) Structural analysis of the voltage-dependent calcium channel β subunit functional core and its complex with the α1 interaction domain. Neuron 42:387–399

  65. Opatowsky Y, Chomsky-Hecht O, Kang M-G, Campbell KP, Hirsch JA (2003) The voltage-dependent calcium channel β subunit contains two stable interacting domains. J Biol Chem 278:52323–52332

  66. Pancaroglu R, Van Petegem F (2018) Calcium channelopathies: structural insights into disorders of the muscle excitation–contraction complex. Annu Rev Genet 52:373–396

  67. Paolini C, Fessenden JD, Pessah IN, Franzini-Armstrong C (2004) Evidence for conformational coupling between two calcium channels. Proc Natl Acad Sci U S A 101:12748–12752

  68. Perez CF, Voss A, Pessah IN, Allen PD (2003) RyR1/RyR3 chimeras reveal that multiple domains of RyR1 are involved in skeletal-type E-C coupling. Biophys J 84:2655–2663

  69. Perni S, Lavorato M, Beam KG (2017) De novo reconstitution reveals the proteins required for skeletal muscle voltage-induced Ca2+ release. Proc Natl Acad Sci U S A 114:13822–13827

  70. Phimister AJ, Lango J, Lee EH, Ernst-Russell MA, Takeshima H, Ma J, Allen PD, Pessah IN (2007) Conformation-dependent stability of junctophilin 1 (JP1) and ryanodine receptor type 1 (RyR1) channel complex is mediated by their hyper-reactive thiols. J Biol Chem 282:8667–8677

  71. Polster A, Nelson BR, Olson EN, Beam KG (2016) Stac3 has a direct role in skeletal muscle-type excitation–contraction coupling that is disrupted by a myopathy-causing mutation. Proc Natl Acad Sci U S A 113:10986–10991

  72. Polster A, Nelson BR, Papadopoulos S, Olson EN, Beam KG (2018) Stac proteins associate with the critical domain for excitation–contraction coupling in the II–III loop of CaV1.1. J Gen Physiol 150:613–624

  73. Polster A, Ohrtman JD, Beam KG, Papadopoulos S (2012) Fluorescence resonance energy transfer (FRET) indicates that association with the type I ryanodine receptor (RyR1) causes reorientation of multiple cytoplasmic domains of the dihydropyridine receptor (DHPR) α1S subunit. J Biol Chem 287:41560–41568

  74. Polster A, Perni S, Bichraoui H, Beam KG (2015) Stac adaptor proteins regulate trafficking and function of muscle and neuronal L-type Ca2+ channels. Proc Natl Acad Sci U S A 112:602–606

  75. Pragnell M, De Waard M, Mori Y, Tanabe T, Snutch TP, Campbell KP (1994) Calcium channel β-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1-subunit. Nature 368:67–70

  76. Proenza C, O'Brien J, Nakai J, Mukherjee S, Allen PD, Beam KG (2002) Identification of a region of RyR1 that participates in allosteric coupling with the α1S (CaV1.1) II–III loop. J Biol Chem 277:6530–6535

  77. Proenza C, Wilkens C, Lorenzon NM, Beam KG (2000a) A carboxyl-terminal region important for the expression and targeting of the skeletal muscle dihydropyridine receptor. J Biol Chem 275:23169–23174

  78. Proenza C, Wilkens CM, Beam KG (2000b) Excitation-contraction coupling is not affected by scrambled sequence in residues 681–690 of the dihydropyridine receptor II-III loop. J Biol Chem 275:29935–29937

  79. Protasi F (2002) Structural interaction between RYRs and DHPRs in calcium release units of cardiac and skeletal muscle cells. Front Biosci 7:d650–d658

  80. Protasi F, Paolini C, Nakai J, Beam KG, Franzini-Armstrong C, Allen PD (2002) Multiple regions of RyR1 mediate functional and structural interactions with α1S-dihydropyridine receptors in skeletal muscle. Biophys J 83:3230–3244

  81. Rebbeck RT, Karunasekara Y, Board PG, Beard NA, Casarotto MG, Dulhunty AF (2014) Skeletal muscle excitation–contraction coupling: who are the dancing partners? Int J Biochem Cell Biol 48:28–38

  82. Rebbeck RT, Karunasekara Y, Gallant EM, Board PG, Beard NA, Casarotto MG, Dulhunty AF (2011) The β1a subunit of the skeletal DHPR binds to skeletal RyR1 and activates the channel via its 35-residue C-terminal tail. Biophys J 100:922–930

  83. Reinholt BM, Ge X, Cong X, Gerrard DE, Jiang H (2013) Stac3 is a novel regulator of skeletal muscle development in mice. PLoS One 8:e62760

  84. Richards MW, Butcher AJ, Dolphin AC (2004) Ca2+ channel β-subunits: structural insights AID our understanding. Trends Pharmacol Sci 25:626–632

  85. Rios E, Brum G (1987) Involvement of dihydropyridine receptors in excitation–contraction coupling in skeletal muscle. Nature 325:717–720

  86. Sandow A (1952) Excitation-contraction coupling in muscular response. Yale J Biol Med 25:176–201

  87. Schredelseker J, Dayal A, Schwerte T, Franzini-Armstrong C, Grabner M (2009) Proper restoration of excitation-contraction coupling in the dihydropyridine receptor β1-null zebrafish relaxed is an exclusive function of the β1a subunit. J Biol Chem 284:1242–1251

  88. Schredelseker J, Di Biase V, Obermair GJ, Felder ET, Flucher BE, Franzini-Armstrong C, Grabner M (2005) The β1a subunit is essential for the assembly of dihydropyridine-receptor arrays in skeletal muscle. Proc Natl Acad Sci U S A 102:17219–17224

  89. Sheridan DC, Cheng W, Carbonneau L, Ahern CA, Coronado R (2004) Involvement of a heptad repeat in the carboxyl terminus of the dihydropyridine receptor β1a subunit in the mechanism of excitation-contraction coupling in skeletal muscle. Biophys J 87:929–942

  90. Sheridan DC, Takekura H, Franzini-Armstrong C, Beam KG, Allen PD, Perez CF (2006) Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions. Proc Natl Acad Sci U S A 103:19760–19765

  91. Strube C, Beurg M, Powers PA, Gregg RG, Coronado R (1996) Reduced Ca2+ current, charge movement, and absence of Ca2+ transients in skeletal muscle deficient in dihydropyridine receptor β1 subunit. Biophys J 71:2531–2543

  92. Tae H-S, Norris NC, Cui Y, Karunasekara Y, Board PG, Dulhunty AF, Casarotto MG (2009) Molecular recognition of the disordered dihydropyridine receptor II-III loop by a conserved SPRY domain of the type 1 ryanodine receptor. Clin Exp Pharmacol Physiol 36:346–349

  93. Takeshima H, Iino M, Takekura H, Nishi M, Kuno J, Minowa O, Takano H, Noda T (1994) Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene. Nature 369:556–559

  94. Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K (2000) Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell 6:11–22

  95. Tanabe T, Beam KG, Adams BA, Niidome T, Numa S (1990) Regions of the skeletal muscle dihydropyridine receptor critical for excitation–contraction coupling. Nature 346:567–569

  96. Tanabe T, Beam KG, Powell JA, Numa S (1988) Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA. Nature 336:134–139

  97. Van Petegem F, Clark KA, Chatelain FC, Minor DL Jr (2004) Structure of a complex between a voltage-gated calcium channel β-subunit and an α-subunit domain. Nature 429:671–675

  98. Weiss RG, O’Connell KMS, Flucher BE, Allen PD, Grabner M, Dirksen RT (2004) Functional analysis of the R1086H malignant hyperthermia mutation in the DHPR reveals an unexpected influence of the III-IV loop on skeletal muscle EC coupling. Am J Physiol: Cell Physiol 287:C1094–C1102

  99. Wilkens CM, Kasielke N, Flucher BE, Beam KG, Grabner M (2001) Excitation–contraction coupling is unaffected by drastic alteration of the sequence surrounding residues L720–L764 of the α1S II-III loop. Proc Natl Acad Sci U S A 98:5892–5897

  100. Wu J, Yan Z, Li Z, Qian X, Lu S, Dong M, Zhou Q, Yan N (2016) Structure of the voltage-gated calcium channel CaV1.1 at 3.6 Å resolution. Nature 537:191–196

  101. Wu J, Yan Z, Li Z, Yan C, Lu S, Dong M, Yan N (2015) Structure of the voltage-gated calcium channel CaV1.1 complex. Science 350:aad2395

  102. Yamazawa T, Takeshima H, Shimuta M, Iino M (1997) A region of the ryanodine receptor critical for excitation-contraction coupling in skeletal muscle. J Biol Chem 272:8161–8164

  103. Yan Z, X-c B, Yan C, Wu J, Li Z, Xie T, Peng W, C-c Y, Li X, Scheres SH, Shi Y, Yan N (2015) Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution. Nature 517:50–55

  104. Yuen SMWK, Campiglio M, Tung C-C, Flucher BE, Van Petegem F (2017) Structural insights into binding of STAC proteins to voltage-gated calcium channels. Proc Natl Acad Sci U S A 114:E9520–E9528

  105. Zaharieva IT et al (2018) STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility. Hum Mutat 39:1980–1994

  106. Zalk R, Clarke OB, des Georges A, Grassucci RA, Reiken S, Mancia F, Hendrickson WA, Frank J, Marks AR (2015) Structure of a mammalian ryanodine receptor. Nature 517:44–49

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Acknowledgements

Investigator Grant fellowship (GNT1173015) to DS from the National Health & Medical Research Council (NHMRC) of Australia is acknowledged. The author would like to thank A/Prof. Marco G. Casarotto and Prof. Angela F. Dulhunty for proofreading the manuscript and many useful discussions on the topic of the review.

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Correspondence to Dmitry Shishmarev.

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Shishmarev, D. Excitation-contraction coupling in skeletal muscle: recent progress and unanswered questions. Biophys Rev (2020). https://doi.org/10.1007/s12551-020-00610-x

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Keywords

  • Excitation-contraction coupling
  • DHPR
  • CaV1.1
  • RyR1
  • STAC3