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

Claudio F. Perez, Santwana Mukherjee, Paul D. Allen

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

To identify domains of the ryanodine receptor (RyR1) that are functionally relevant for excitation-contraction (EC) coupling in vivo, we have studied the ability of RyR1/RyR3 chimera to rescue skeletal EC coupling in dyspedic myotubes. In this work we show that chimeric receptors containing amino acids 1-1,680 of RyR1 were able to render depolarization-induced Ca2+ release to RyR3. Within this region, residues 1,272-1,455, containing divergent domain D2 of RyR1, proved to be a critical element because the absence of this region selectively abolished depolarization-evoked Ca2+ transients without affecting chemically induced activation. Although the D2 domain by itself failed to restore skeletal EC coupling to RyR3, the addition of the D2 region resulted in a dramatic enhancement of EC coupling restored by an RyR3 chimera containing amino acids 1,681-3,770 of RyR1. These results suggest that although the D2 domain of RyR1 plays a key role during EC coupling, additional region(s) from the N-terminal end of RyR1 as well as previously identified regions of the central portion of the receptor are needed in order to allow normal EC coupling.

Original languageEnglish (US)
Pages (from-to)39644-39652
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number41
DOIs
StatePublished - Oct 10 2003
Externally publishedYes

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Excitation Contraction Coupling
Ryanodine Receptor Calcium Release Channel
Amino Acids
Depolarization
Amino Acid Receptors
Skeletal Muscle Fibers

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Perez, Claudio F.; Mukherjee, Santwana; Allen, Paul D.

In: Journal of Biological Chemistry, Vol. 278, No. 41, 10.10.2003, p. 39644-39652.

Research output: Contribution to journalArticle

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