Twitches in the presence of ethylene glycol bis(β-aminoethyl ether)-N,N′-tetraacetic acid

Armstrong, Clay M.; Bezanilla, Francisco; Horowicz, Paul

doi:10.1016/0005-2728(72)90194-6

Cited by 389 publications

(244 citation statements)

References 9 publications

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“…Thus, cardiac E-C coupling is dependent on extracellular Ca 2þ and functional coupling between Ca v 1.2 and RyR2, which is assumed to rely on spatial proximity between the proteins rather than physical interaction. Because of the role of the direct physical interaction between Ca V 1.1 and RyR1 in skeletal muscle, E-C coupling can proceed for long periods in the absence of extracellular Ca 2þ (Armstrong CM 1972;Dulhunty and Gage 1988). The Ca V 1.1 and RyR1 interaction in skeletal muscle is dependent on the strict geometrical alignments between the two proteins, which has been shown with electron microscopy in different muscle preparations (Takekura et al 1994;Protasi et al 1998) A critical determinant of E-C coupling in skeletal muscle is the a 1S II-III loop of Ca v 1.1, with a minor involvement of the a 1S I-II loop (Tanabe et al 1990;Nakai et al 1998;Kugler et al 2004).…”

Section: Crystal Structure Of the Amino-terminal Domainmentioning

confidence: 99%

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Lanner¹,

Georgiou²,

Joshi³

et al. 2010

Cold Spring Harbor Perspectives in Biology

655

572

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Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca 2þ from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle. RyRs are the largest known ion channels (.2MDa) and exist as three mammalian isoforms (RyR 1 -3), all of which are homotetrameric proteins that interact with and are regulated by phosphorylation, redox modifications, and a variety of small proteins and ions. Most RyR channel modulators interact with the large cytoplasmic domain whereas the carboxy-terminal portion of the protein forms the ion-conducting pore. Mutations in RyR2 are associated with human disorders such as catecholaminergic polymorphic ventricular tachycardia whereas mutations in RyR1 underlie diseases such as central core disease and malignant hyperthermia. This chapter examines the current concepts of the structure, function and regulation of RyRs and assesses the current state of understanding of their roles in associated disorders.

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Section: Crystal Structure Of the Amino-terminal Domainmentioning

confidence: 99%

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Lanner¹,

Georgiou²,

Joshi³

et al. 2010

Cold Spring Harbor Perspectives in Biology

655

572

View full text Add to dashboard Cite

show abstract

“…These voltage-dependent conformational changes result in (i) activation of the L-type Ca 2+ current and (ii) the activation of Ca 2+ release from the sarcoplasmic reticulum (SR) via type 1 ryanodine receptors (RyR1). Importantly, activation of RyR1 in skeletal muscle does not depend on the L-type Ca 2+ current but, rather, is linked directly to the conformational changes of the Ltype channels ("conformational coupling") (4,7,8).…”

Section: 4-dihydropyridine Receptor | α Ismentioning

confidence: 99%

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Eltit

Bannister²,

Moua

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Malignant hyperthermia (MH) susceptibility is a dominantly inherited disorder in which volatile anesthetics trigger aberrant Ca 2+ release in skeletal muscle and a potentially fatal rise in perioperative body temperature. Mutations causing MH susceptibility have been identified in two proteins critical for excitation-contraction (EC) coupling, the type 1 ryanodine receptor (RyR1) and Ca V 1.1, the principal subunit of the L-type Ca 2+ channel. All of the mutations that have been characterized previously augment EC coupling and/or increase the rate of L-type Ca 2+ entry. The Ca V 1.1 mutation R174W associated with MH susceptibility occurs at the innermost basic residue of the IS4 voltage-sensing helix, a residue conserved among all Ca V channels [Carpenter D, et al. (2009) BMC Med Genet 10:104-115.]. To define the functional consequences of this mutation, we expressed it in dysgenic (Ca V 1.1 null) myotubes. Unlike previously described MH-linked mutations in Ca V 1.1, R174W ablated the L-type current and had no effect on EC coupling. Nonetheless, R174W increased sensitivity of Ca 2+ release to caffeine (used for MH diagnostic in vitro testing) and to volatile anesthetics. Moreover, in Ca V 1.1 R174W-expressing myotubes, resting myoplasmic Ca 2+ levels were elevated, and sarcoplasmic reticulum (SR) stores were partially depleted, compared with myotubes expressing wild-type Ca V 1.1. Our results indicate that Ca V 1.1 functions not only to activate RyR1 during EC coupling, but also to suppress resting RyR1-mediated Ca 2+ leak from the SR, and that perturbation of Ca V 1.1 negative regulation of RyR1 leak identifies a unique mechanism that can sensitize muscle cells to MH triggers.

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“…In the junctional membrane, DHPRs are arrayed in groups of four ("tetrads") as a consequence of physical links with RyR1 (5,6). The existence of these links and the fact that skeletal-type EC coupling does not require the entry of external Ca 2ϩ have led to the idea that conformational changes of the linking regions are responsible for the activation of RyR1 (7,8). However, the identity of the linking regions has remained obscure in large measure because the interaction takes place between two separate membrane systems and depends upon voltage across the plasma membrane.…”

mentioning

confidence: 99%

Fluorescence Resonance Energy Transfer (FRET) Indicates That Association with the Type I Ryanodine Receptor (RyR1) Causes Reorientation of Multiple Cytoplasmic Domains of the Dihydropyridine Receptor (DHPR) α1S Subunit

Polster

Ohrtman

Beam

et al. 2012

Journal of Biological Chemistry

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Twitches in the presence of ethylene glycol bis(β-aminoethyl ether)-N,N′-tetraacetic acid

Cited by 389 publications

References 9 publications

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor

Fluorescence Resonance Energy Transfer (FRET) Indicates That Association with the Type I Ryanodine Receptor (RyR1) Causes Reorientation of Multiple Cytoplasmic Domains of the Dihydropyridine Receptor (DHPR) α1S Subunit

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Twitches in the presence of ethylene glycol bis(β-aminoethyl ether)-N,N′-tetraacetic acid

Cited by 389 publications

References 9 publications

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca 2+ channel and the type 1 ryanodine receptor

Fluorescence Resonance Energy Transfer (FRET) Indicates That Association with the Type I Ryanodine Receptor (RyR1) Causes Reorientation of Multiple Cytoplasmic Domains of the Dihydropyridine Receptor (DHPR) α1S Subunit

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Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca ²⁺ channel and the type 1 ryanodine receptor