Calcium ions (Ca2+) are essential signaling molecules and must be carefully regulated to preserve specificity in function. One indispensible Ca2+ signaling protein is the ryanodine receptor (RyR) calcium release channel. RyR1 is essential for muscle contraction, and RyR1mutations can lead to severe muscle disorders such as malignant hyperthermia (MH). Recently, a mouse model of human MH (Y522S-RyR1) has been developed. In skeletal muscle, Y522S-RyR1 exhibits an increased sensitivity to activation resulting in Ca2+ leak, mitochondrial disorganization, and cellular stress. Although RyR1 expression is limited in the brain, the cerebellum may be particularly vulnerable to this disease because RyR1 is highly expressed in Purkinje neurons. In this study, Y522S-RyR1 in Purkinje cells exhibits a lower threshold for activation, but does not cause severe cellular stress and damage. Future investigation of compensatory mechanisms for increased Ca2+ release in Purkinje cells could be of therapeutic value for many neurological and muscular disorders.
","abstract_html":"<p>Calcium ions (Ca2+) are essential signaling molecules and must be carefully regulated to preserve specificity in function. One indispensible Ca2+ signaling protein is the ryanodine receptor (RyR) calcium release channel. RyR1 is essential for muscle contraction, and RyR1mutations can lead to severe muscle disorders such as malignant hyperthermia (MH). Recently, a mouse model of human MH (Y522S-RyR1) has been developed. In skeletal muscle, Y522S-RyR1 exhibits an increased sensitivity to activation resulting in Ca2+ leak, mitochondrial disorganization, and cellular stress. Although RyR1 expression is limited in the brain, the cerebellum may be particularly vulnerable to this disease because RyR1 is highly expressed in Purkinje neurons. In this study, Y522S-RyR1 in Purkinje cells exhibits a lower threshold for activation, but does not cause severe cellular stress and damage. Future investigation of compensatory mechanisms for increased Ca2+ release in Purkinje cells could be of therapeutic value for many neurological and muscular disorders.</p>","abstract_has_math":false,"creators":["Santiago, Jason"],"institution":null,"degree_name":"M.S.","degree_level":"Masters Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Nancy M. Lorenzon, Ph.D.","Joseph Angleson","Daniel Linseman"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-01T08:00:00Z","date_published":"2010-01-01T08:00:00Z","updated_at":"2026-07-24T02:02:19Z","subjects":["Calcium dysregulation","Malignant hyperthermia","Oxidative stress","Purkinje cell","Ryanodine receptor","Biology","Cell and Developmental Biology","Life Sciences"],"languages":["en"],"rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.du.edu/etd/574","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nancy M. Lorenzon, Ph.D.","Joseph Angleson","Daniel Linseman"]},{"key":"dc:creator","label":"Author","values":["Santiago, Jason"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2001-01-01T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Calcium dysregulation","Malignant hyperthermia","Oxidative stress","Purkinje cell","Ryanodine receptor","Biology","Cell and Developmental Biology","Life Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is held by the author. User is responsible for all copyright compliance.
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"],"dc:format":["application/pdf"],"dc:identifier":["https://digitalcommons.du.edu/etd/574"],"dc:language":["en"],"dc:rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"dc:subject":["Calcium dysregulation","Malignant hyperthermia","Oxidative stress","Purkinje cell","Ryanodine receptor","Biology","Cell and Developmental Biology","Life Sciences"],"dc:title":["Neuronal Calcium Regulation and Cellular Stress in a Malignant Hyperthermia Disease Model"],"thesis:degree_level":["Masters Thesis"],"thesis:degree_name":["M.S."]},"updated_at":"2026-07-24T02:02:19Z"}