A malignant hyperthermia-inducing mutation in RYR1 (R163C): Consequent alterations in the functional properties of DHPR channels
Author
dc.contributor.author
Bannister, Roger A.
Author
dc.contributor.author
Estève, Eric
Author
dc.contributor.author
Eltit Ortega, José Miguel
Author
dc.contributor.author
Pessah, Isaac N.
Author
dc.contributor.author
Allen, Paul D.
Author
dc.contributor.author
López, José R.
Author
dc.contributor.author
Beam, Kurt G.
Admission date
dc.date.accessioned
2019-03-11T12:59:23Z
Available date
dc.date.available
2019-03-11T12:59:23Z
Publication date
dc.date.issued
2010
Cita de ítem
dc.identifier.citation
Journal of General Physiology, Volumen 135, Issue 6, 2018, Pages 629-640
Identifier
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00221295
Identifier
dc.identifier.issn
15407748
Identifier
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10.1085/jgp.200910329
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/165001
Abstract
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Bidirectional communication between the 1,4-dihydropyridine receptor (DHPR) in the plasma membrane and the type 1 ryanodine receptor (RYR1) in the sarcoplasmic reticulum (SR) is responsible for both skeletal-type excitation-contraction coupling (voltage-gated Ca2+ release from the SR) and increased amplitude of L-type Ca2+ current via the DHPR. Because the DHPR and RYR1 are functionally coupled, mutations in RYR1 that are linked to malignant hyperthermia (MH) may affect DHPR activity. For this reason, we investigated whether cultured myotubes originating from mice carrying an MH-linked mutation in RYR1 (R163C) had altered voltage-gated Ca2+ release from the SR, membrane-bound charge movement, and/or L-type Ca 2+ current. In myotubes homozygous (Horn) for the R163C mutation, voltage-gated Ca2+ release from the SR was substantially reduced and shifted (∼10 mV) to more hyperpolarizing potentials compared with wild-type (WT) myotubes. Intramembrane charge movements of both Hom and heterozy