Multiple regions of RyR1 mediate functional and structural interactions with α1S-dihydropyridine receptors in skeletal muscle

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

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


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: α1SDHPRs 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 α1SDHPRs. α1SDHPR and RyR1 are linked to each other, organizing α1S-DHPRs into groups of four, or tetrads. In cardiac muscle, however, α1CDHPR Ca2+ current is important for activation of RyR2 (the cardiac isoform of the ryanodine receptor) and α1C-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 α1SDHPRs and that the regions responsible for tetrad formation do not correspond exactly to the ones required for functional coupling.

Original languageEnglish (US)
Pages (from-to)3230-3244
Number of pages15
JournalBiophysical Journal
Issue number6
StatePublished - Dec 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics


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