Distinct immunopeptide maps of the sarcoplasmic reticulum Ca2+ release channel in malignant hyperthermia

C Michael Knudson; James R Mickelson; Charles F Louis; Kevin P Campbell

doi:10.1016/S0021-9258(19)39813-8

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Distinct immunopeptide maps of the sarcoplasmic reticulum Ca2+ release channel in malignant hyperthermia

Journal article

Open access

Peer reviewed

Distinct immunopeptide maps of the sarcoplasmic reticulum Ca2+ release channel in malignant hyperthermia

C Michael Knudson, James R Mickelson, Charles F Louis and Kevin P Campbell

The Journal of biological chemistry, Vol.265(5), pp.2421-2424

1990

DOI: 10.1016/S0021-9258(19)39813-8

PMID: 2154446

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Abstract

Sarcoplasmic reticulum isolated from malignant hyperthermia-susceptible (MHS) muscle exhibits abnormalities in the regulation of calcium release. To identify the molecular basis of this abnormality, the Ca2+ release channel from both normal and MHS sarcoplasmic reticulum was examined using proteolytic digestion followed by immunoblot staining with a polyclonal antibody against the rabbit Ca2+ release channel protein. Under appropriate conditions, trypsin digestion of isolated sarcoplasmic reticulum vesicles from the two types of pigs revealed a distinct difference in the immunostaining pattern of the Ca2+ release channel-derived peptides. An approximate 86-kDa peptide was the predominant fragment in normal sarcoplasmic reticulum while an approximate 99-kDa peptide fragment was the major peptide detected in MHS sarcoplasmic reticulum. Digestion of sarcoplasmic reticulum vesicles isolated from four normal and four MHS pigs showed that the differences were highly reproducible. Trypsin digestion of sarcoplasmic reticulum isolated from heterozygous pigs, which contain one normal and one MHS allele, showed an antibody staining pattern that was intermediate between MHS and normal sarcoplasmic reticulum. These results can be explained by a primary amino acid sequence difference between the normal and MHS Ca2+ release channels and support the hypothesis that a mutation in the gene coding for the sarcoplasmic reticulum Ca2+ release channel is responsible for malignant hyperthermia.

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Molecular and cellular biology

Cell structures and functions

Cell membranes. Ionic channels. Membrane pores

Details

Title: Subtitle: Distinct immunopeptide maps of the sarcoplasmic reticulum Ca2+ release channel in malignant hyperthermia
Creators: C Michael Knudson - Howard Hughes medical inst., Iowa City IA 52242, United States
James R Mickelson - Howard Hughes medical inst., Iowa City IA 52242, United States
Charles F Louis - Howard Hughes medical inst., Iowa City IA 52242, United States
Kevin P Campbell - Howard Hughes medical inst., Iowa City IA 52242, United States
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.265(5), pp.2421-2424
DOI: 10.1016/S0021-9258(19)39813-8
PMID: 2154446
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; Bethesda, MD
Language: English
Date published: 1990
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Radiation Oncology
Record Identifier: 9984047651902771

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