Skeletal muscle excitation-contraction coupling: Who are the dancing partners?

Robyn T. Rebbeck, Yamuna Karunasekara, Philip G. Board, Nicole A. Beard, Marco G. Casarotto, Angela F. Dulhunty

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations


There is an overwhelming body of work supporting the idea that excitation-contraction coupling in skeletal muscle depends on a physical interaction between the skeletal muscle isoform of the dihydropyridine receptor L-type Ca2+ channel and the skeletal isoform of the ryanodine receptor Ca2+ release channel. A general assumption is that this physical interaction is between "critical" residues that have been identified in the II-III loop of the dihydropyridine receptor alpha subunit and the ryanodine receptor. However, despite extensive searches, the complementary "critical" residues in the ryanodine receptor have not been identified. This raises the possibility that the coupling proceeds either through other subunits of the dihydropyridine receptor and/or other co-proteins within the large RyR1 protein complex. There have been some remarkable advances in recent years in identifying proteins in the RyR complex that impact on the coupling process, and these are considered in this review. A major candidate for a role in the coupling mechanism is the beta subunit of the dihydropyridine receptor, because specific residues in both the beta subunit and ryanodine receptor have been identified that facilitate an interaction between the two proteins and these also impact on excitation-contraction coupling. This role of beta subunit remains to be fully investigated as well as the degree to which it may complement any other direct or indirect voltage-dependent coupling interactions between the DHPR alpha II-III loop and the ryanodine receptor.

Original languageEnglish (US)
Pages (from-to)28-38
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Issue number1
StatePublished - Mar 2014
Externally publishedYes


  • Dihydropyridine receptor
  • Excitation-contraction coupling
  • Ryanodine receptor
  • Sarcoplasmic reticulum
  • Skeletal muscle


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