Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels

Junichi Nakai, Naomi Sekiguchi, Thomas A. Rando, Paul D. Allen, Kurt G. Beam

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Ryanodine receptors (RyRs) are present in the endoplasmic reticulum of virtually every cell type and serve critical roles, including excitation- contraction (EC) coupling in muscle cells. In skeletal muscle the primary control of RyR-1 (the predominant skeletal RyR isoform) occurs via an interaction with plasmalemmal dihydropyridine receptors (DHPRs), which function as both voltage sensors for EC coupling and as L-type Ca2+ channels (Rios, E., and Bruin, G. (1987) Nature 325, 717-720). In addition to 'receiving' the EC coupling signal from the DHPR, RyR-1 also 'transmits' a retrograde signal that enhances the Ca2+ channel activity of the DHPR (Nakai, J., Dirksen, R. T., Nguyen, H. T., Pessah, I. N., Beam, K. G., and Allen, P. D. (1996) Nature 380, 72-76). A similar kind of retrograde signaling (from RyRs to L-type Ca2+ channels) has also been reported in neurons (Chavis, P., Fagni, L, Lansman, J. B., and Bockaert, J. (1996) Nature 382, 719-722). To investigate the molecular mechanism of reciprocal signaling, we constructed cDNAs encoding chimeras of RyR-1 and RyR-2 (the predominant cardiac RyR isoform) and expressed them in dyspedic myotubes, which lack an endogenous RyR-1. We found that a chimera that contained residues 1,635-2,636 of RyR-1 both mediated skeletal-type EC coupling and enhanced Ca2+ channel function, whereas a chimera containing adjacent RyR- 1 residues (2,659-3,720) was only able to enhance Ca2+ channel function. These results demonstrate that two distinct regions are involved in the reciprocal interactions of RyR-1 with the skeletal DHPR.

Original languageEnglish (US)
Pages (from-to)13403-13406
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number22
DOIs
StatePublished - May 29 1998
Externally publishedYes

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Excitation Contraction Coupling
L-Type Calcium Channels
Ryanodine Receptor Calcium Release Channel
Muscle
Protein Isoforms
Skeletal Muscle Fibers
Endoplasmic Reticulum
Muscle Cells
Neurons
Skeletal Muscle
Complementary DNA
Cells
Sensors
Electric potential

ASJC Scopus subject areas

  • Biochemistry

Cite this

Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels. / Nakai, Junichi; Sekiguchi, Naomi; Rando, Thomas A.; Allen, Paul D.; Beam, Kurt G.

In: Journal of Biological Chemistry, Vol. 273, No. 22, 29.05.1998, p. 13403-13406.

Research output: Contribution to journalArticle

Nakai, Junichi ; Sekiguchi, Naomi ; Rando, Thomas A. ; Allen, Paul D. ; Beam, Kurt G. / Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 22. pp. 13403-13406.
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