Artículos de revistas
A malignant hyperthermia-inducing mutation in RYR1 (R163C): Consequent alterations in the functional properties of DHPR channels
Fecha
2010Registro en:
Journal of General Physiology, Volumen 135, Issue 6, 2018, Pages 629-640
00221295
15407748
10.1085/jgp.200910329
Autor
Bannister, Roger A.
Estève, Eric
Eltit Ortega, José Miguel
Pessah, Isaac N.
Allen, Paul D.
López, José R.
Beam, Kurt G.
Institución
Resumen
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