98 research outputs found

    β Subunit M2–M3 Loop Conformational Changes Are Uncoupled from α1 β Glycine Receptor Channel Gating: Implications for Human Hereditary Hyperekplexia

    Get PDF
    Hereditary hyperekplexia, or startle disease, is a neuromotor disorder caused mainly by mutations that either prevent the surface expression of, or modify the function of, the human heteromeric α1 β glycine receptor (GlyR) chloride channel. There is as yet no explanation as to why hyperekplexia mutations that modify channel function are almost exclusively located in the α1 to the exclusion of β subunit. The majority of these mutations are identified in the M2–M3 loop of the α1 subunit. Here we demonstrate that α1 β GlyR channel function is less sensitive to hyperekplexia-mimicking mutations introduced into the M2–M3 loop of the β than into the α1 subunit. This suggests that the M2–M3 loop of the α subunit dominates the β subunit in gating the α1 β GlyR channel. A further attempt to determine the possible mechanism underlying this phenomenon by using the voltage-clamp fluorometry technique revealed that agonist-induced conformational changes in the β subunit M2–M3 loop were uncoupled from α1 β GlyR channel gating. This is in contrast to the α subunit, where the M2–M3 loop conformational changes were shown to be directly coupled to α1 β GlyR channel gating. Finally, based on analysis of α1 β chimeric receptors, we demonstrate that the structural components responsible for this are distributed throughout the β subunit, implying that the β subunit has evolved without the functional constraint of a normal gating pathway within it. Our study provides a possible explanation of why hereditary hyperekplexia-causing mutations that modify α1 β GlyR channel function are almost exclusively located in the α1 to the exclusion of the β subunit

    Ãœber die90Sr-Kontamination von menschlichen Geweben und einer Standardnahrung

    No full text

    Zur Kontamination der menschlichen Placenta durch90Sr

    No full text

    90Sr-Gehalt der menschlichen Placenta und der Neugeborenenknochen

    No full text

    �ber den90Sr-Gehalt menschlicher Knochen in den Jahren 1958 und 1959

    No full text

    A new allele of ak-polymorphism: AK0

    No full text

    Au�ergew�hnlicher Verlauf einer Vergiftung mit E 605-Spritzpulver

    No full text

    Suicide by intravenous injection of mercury bichloride solution

    No full text
    • …
    corecore