| Stimulation and inhibition of [3H]ryanodine binding to sarcoplasmic reticulum from malignant hyperthermia susceptible pigs. | |
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MedLine Citation:
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PMID: 2321964 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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When compared to normal pig sarcoplasmic reticulum (SR), SR from malignant hyperthermia susceptible (MHS) porcine skeletal muscle has been shown to exhibit an increased rate of calcium release, as well as alterations in [3H]ryanodine-binding activity in the presence of microM Ca2+ (Mickelson et al., 1988, J. Biol. Chem. 263, 9310). In the present study, various stimulators (adenine nucleotides and caffeine) and inhibitors (ruthenium red and Mg2+) of the SR calcium release channel were examined for effects on MHS and normal SR [3H]ryanodine binding. The apparent affinity of the MHS SR receptor for ryanodine in the presence of 10 mM ATP (Kd = 6.0 nM) or 10 mM caffeine (Kd = 28 nM) was significantly greater than that of the normal SR (Kd = 8.5 and 65 nM in 10 mM ATP or caffeine, respectively), the Bmax (12-16 pmol/mg) was similar in all cases. The Ca2+(0.5) for inhibition of [3H]ryanodine binding in the presence of 5 mM AMPPNP (238 vs 74 microM for MHS and normal SR, respectively) and the Ca2+(0.5) for stimulation of [3H]ryanodine binding in the presence of 5 mM caffeine (0.049 vs 0.070 microM for MHS and normal SR, respectively) were also significantly different. Furthermore, in the presence of optimal Ca2+, MHS SR [3H]ryanodine binding was more sensitive to caffeine stimulation (C0.5 of 1.7 vs 3.4 mM) and was less sensitive to ruthenium red (C0.5 of 1.9 vs 1.2 microM) or Mg2+ inhibition (C0.5 of 0.34 vs 0.21 mM) than was normal SR. These results further support the hypothesis that differences in the ryanodine/receptor calcium release channel regulatory properties are responsible for the abnormal calcium releasing activity of MHS SR. |
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Authors:
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J R Mickelson; L A Litterer; B A Jacobson; C F Louis |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 278 ISSN: 0003-9861 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 1990 Apr |
Date Detail:
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Created Date: 1990-05-04 Completed Date: 1990-05-04 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 251-7 Citation Subset: IM |
Affiliation:
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Department of Veterinary Biology, University of Minnesota, St. Paul 55108. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenylyl Imidodiphosphate
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pharmacology Alkaloids / metabolism* Animals Caffeine / pharmacology Calcium / pharmacology Kinetics Magnesium / pharmacology Malignant Hyperthermia / genetics, metabolism, veterinary* Muscles / metabolism* Receptors, Cholinergic / drug effects, metabolism* Reference Values Ryanodine / metabolism* Ryanodine Receptor Calcium Release Channel Sarcoplasmic Reticulum / metabolism* Swine Swine Diseases / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GM-31382/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Alkaloids; 0/Receptors, Cholinergic; 0/Ryanodine Receptor Calcium Release Channel; 15662-33-6/Ryanodine; 25612-73-1/Adenylyl Imidodiphosphate; 58-08-2/Caffeine; 7439-95-4/Magnesium; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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