Biophys J, December 2002, p. 3230-3244, Vol. 83, No. 6

Multiple Regions of RyR1 Mediate Functional and Structural Interactions with _1S-Dihydropyridine Receptors in Skeletal Muscle

Feliciano Protasi,^* Cecilia Paolini, Junichi Nakai, Kurt G. Beam,^§ Clara Franzini-Armstrong, and Paul D. Allen^*

 ^*Department of Anesthesia Research, Brigham and Women's Hospital, Boston, Massachusetts 02115 USA;  Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 USA;  National Institute for Physiological Sciences, Okazaki 444, Japan; and  ^§Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523 USA

Excitation-contraction (e-c) coupling in muscle relies on the interaction between dihydropyridine receptors (DHPRs) and RyRs within Ca²⁺ release units (CRUs). In skeletal muscle this interaction is bidirectional: _1SDHPRs trigger RyR1 (the skeletal form of the ryanodine receptor) to release Ca²⁺ in the absence of Ca²⁺ permeation through the DHPR, and RyR1s, in turn, affect the open probability of _1SDHPRs. _1SDHPR and RyR1 are linked to each other, organizing _1S-DHPRs into groups of four, or tetrads. In cardiac muscle, however, _1CDHPR Ca²⁺ current is important for activation of RyR2 (the cardiac isoform of the ryanodine receptor) and _1C-DHPRs are not organized into tetrads. We expressed RyR1, RyR2, and four different RyR1/RyR2 chimeras (R4: Sk1635-3720, R9: Sk2659-3720, R10: Sk1635-2559, R16: Sk1837-2154) in 1B5 dyspedic myotubes to test their ability to restore skeletal-type e-c coupling and DHPR tetrads. The rank-order for restoring skeletal e-c coupling, indicated by Ca²⁺ transients in the absence of extracellular Ca²⁺, is RyR1 > R4 > R10 R16 > R9 RyR2. The rank-order for restoration of DHPR tetrads is RyR1 > R4 = R9 > R10 = R16 RyR2. Because the skeletal segment in R9 does not overlap with that in either R10 or R16, our results indicate that multiple regions of RyR1 may interact with _1SDHPRs and that the regions responsible for tetrad formation do not correspond exactly to the ones required for functional coupling.

Biophys J, December 2002, p. 3230-3244, Vol. 83, No. 6
© 2002 by the Biophysical Society   0006-3495/02/12/3230/15  $2.00

This article has been cited by other articles:

				H. Balghi, S. Sebille, B. Constantin, S. Patri, V. Thoreau, L. Mondin, E. Mok, A. Kitzis, G. Raymond, and C. Cognard Mini-dystrophin Expression Down-regulates Overactivation of G Protein-mediated IP3 Signaling Pathway in Dystrophin-deficient Muscle Cells J. Gen. Physiol., January 30, 2006; 127(2): 171 - 182. [Abstract] [Full Text] [PDF]

				V. Di Biase and C. Franzini-Armstrong Evolution of skeletal type e-c coupling: a novel means of controlling calcium delivery J. Cell Biol., November 21, 2005; 171(4): 695 - 704. [Abstract] [Full Text] [PDF]

				A. M. Hurne, J. J. O'Brien, D. Wingrove, G. Cherednichenko, P. D. Allen, K. G. Beam, and I. N. Pessah Ryanodine Receptor Type 1 (RyR1) Mutations C4958S and C4961S Reveal Excitation-coupled Calcium Entry (ECCE) Is Independent of Sarcoplasmic Reticulum Store Depletion J. Biol. Chem., November 4, 2005; 280(44): 36994 - 37004. [Abstract] [Full Text] [PDF]

				X. Altafaj, W. Cheng, E. Esteve, J. Urbani, D. Grunwald, J.-M. Sabatier, R. Coronado, M. De Waard, and M. Ronjat Maurocalcine and Domain A of the II-III Loop of the Dihydropyridine Receptor Cav 1.1 Subunit Share Common Binding Sites on the Skeletal Ryanodine Receptor J. Biol. Chem., February 11, 2005; 280(6): 4013 - 4016. [Abstract] [Full Text] [PDF]

				H. Takekura, C. Paolini, C. Franzini-Armstrong, G. Kugler, M. Grabner, and B. E. Flucher Differential Contribution of Skeletal and Cardiac II-III Loop Sequences to the Assembly of Dihydropyridine-Receptor Arrays in Skeletal Muscle Mol. Biol. Cell, December 1, 2004; 15(12): 5408 - 5419. [Abstract] [Full Text] [PDF]

				C. Paolini, J. D. Fessenden, I. N. Pessah, and C. Franzini-Armstrong Evidence for conformational coupling between two calcium channels PNAS, August 24, 2004; 101(34): 12748 - 12752. [Abstract] [Full Text] [PDF]

				G. Kugler, R. G. Weiss, B. E. Flucher, and M. Grabner Structural Requirements of the Dihydropyridine Receptor {alpha}1S II-III Loop for Skeletal-type Excitation-Contraction Coupling J. Biol. Chem., February 6, 2004; 279(6): 4721 - 4728. [Abstract] [Full Text] [PDF]

				A. Shtifman, C. Paolini, J. R. Lopez, P. D. Allen, and F. Protasi Ca2+ influx through {alpha}1S DHPR may play a role in regulating Ca2+ release from RyR1 in skeletal muscle Am J Physiol Cell Physiol, January 1, 2004; 286(1): C73 - C78. [Abstract] [Full Text] [PDF]

				E. H. Lee, J. R. Lopez, J. Li, F. Protasi, I. N. Pessah, D. H. Kim, and P. D. Allen Conformational coupling of DHPR and RyR1 in skeletal myotubes is influenced by long-range allosterism: evidence for a negative regulatory module Am J Physiol Cell Physiol, January 1, 2004; 286(1): C179 - C189. [Abstract] [Full Text] [PDF]

				C. F. Perez, S. Mukherjee, and P. D. Allen Amino Acids 1-1,680 of Ryanodine Receptor Type 1 Hold Critical Determinants of Skeletal Type for Excitation-Contraction Coupling: ROLE OF DIVERGENCE DOMAIN D2 J. Biol. Chem., October 10, 2003; 278(41): 39644 - 39652. [Abstract] [Full Text] [PDF]

				J. D. Fessenden, C. F. Perez, S. Goth, I. N. Pessah, and P. D. Allen Identification of a Key Determinant of Ryanodine Receptor Type 1 Required for Activation by 4-Chloro-m-cresol J. Biol. Chem., August 1, 2003; 278(31): 28727 - 28735. [Abstract] [Full Text] [PDF]

				C. F. Perez, A. Voss, I. N. Pessah, and P. D. Allen RyR1/RyR3 Chimeras Reveal that Multiple Domains of RyR1 Are Involved in Skeletal-Type E-C Coupling Biophys. J., April 1, 2003; 84(4): 2655 - 2663. [Abstract] [Full Text] [PDF]