INT170517

Context Info Confidence 0.15 First Reported 2001 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 2 Total Number 4 Disease Relevance 0.36 Pain Relevance 0.05

cytoplasm (Ryr1, Qdpr) cytosol (Qdpr) mitochondrion (Qdpr) transport (Ryr1) oxidoreductase activity (Qdpr) plasma membrane (Ryr1)

Anatomy Link Frequency myotubes 1 Ryr1 (Mus musculus) Qdpr (Mus musculus) Ryr1 - R163C (1)

Pain Link Frequency Relevance Heat agonist 15 93.52 halothane 6 25.68 addiction 50 5.00 tetrodotoxin 4 5.00 withdrawal 3 5.00 Glutamate 1 5.00 imagery 1 5.00

Disease Link Frequency Relevance Heat Malignant Hyperthermia 45 98.44 Disease 3 34.52 Contracture 6 27.16 Myelodysplastic Syndromes 3 5.00 Congenital Anomalies 3 5.00 Targeted Disruption 2 5.00 Cold Sores 1 5.00 Herpes Simplex Virus 1 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Because the DHPR and RYR1 are functionally coupled, mutations in RYR1 that are linked to malignant hyperthermia (MH) may affect DHPR activity.

RYR1 Binding (coupled) of DHPR associated with malignant hyperthermia

1) Confidence 0.15 Published 2010 Journal The Journal of General Physiology Section Abstract Doc Link PMC2888063 Disease Relevance 0.36 Pain Relevance 0

If this idea is correct, then just as the transition of the DHPR from resting to ECC activated would promote the corresponding transition of RYR1, alterations of RYR1 that promoted its entry into the ECC-activated conformation would facilitate the corresponding transition of the DHPR.

RYR1 Binding (alterations) of DHPR

2) Confidence 0.14 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2888063 Disease Relevance 0 Pain Relevance 0.05

Collectively, the results with whole cell voltage clamp measurements in this paper, and the results on myoplasmic Ca2+ transients evoked by application of elevated K+ to intact myotubes, which are described by Estève et al. in this issue, indicate that the R163C mutation in RYR1 alters the gating of the DHPR with respect both to membrane currents and ECC.

RYR1 (R163C) Binding (gating) of DHPR in myotubes

3) Confidence 0.14 Published 2010 Journal The Journal of General Physiology Section Body Doc Link PMC2888063 Disease Relevance 0 Pain Relevance 0

Further, the interactions between DHPR subunits and RyR1 also are incompletely understood.

RyR1 Binding (interactions) of DHPR

4) Confidence 0.13 Published 2001 Journal BMC Physiol Section Body Doc Link PMC37314 Disease Relevance 0 Pain Relevance 0

General Comments

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