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  • Title: Ca2+ release channels of pigs heterozygous for malignant hyperthermia.
    Author: Shomer NH, Mickelson JR, Louis CF.
    Journal: Muscle Nerve; 1995 Oct; 18(10):1167-76. PubMed ID: 7659111.
    Abstract:
    Porcine malignant hyperthermia (MH) is an autosomal recessive disorder resulting from a mutation in the skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel. The Ca2+ release properties of SR vesicles isolated from pigs heterozygous for the MH gene have been demonstrated previously to be intermediate to those of vesicles isolated from MH-susceptible (MHS) and normal pigs. The Ca2+ release channel is tetrameric, so the intermediate Ca2+ release properties of heterozygous pig SR preparations could result either from populations of MHS and normal homotetramers, or populations of heterotetrameric Ca2+ release channels with properties unique from those of the two types of homozygous channels. To discriminate between these possibilities, the single channel percent open time (Po) and channel dwell time distributions of SR Ca2+ release channels were analyzed. These data suggest that the heterozygous porcine Ca2+ release channel population must contain heterotetramers with properties distinct from those of either MHS or normal channels. The data also imply that the Ca2+ release channel population in MHS humans who are heterozygous for a dominant mutation in this protein also contains heterotetrameric channels.
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