Neuronal Calcium Regulation and Cellular Stress in a Malignant Hyperthermia Disease Model

<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>

Name thesis:degree_name

M.S.

Level thesis:degree_level

Masters Thesis

Year dc:date.available

2010

Author dc:creator

• Santiago, Jason

Contributors dc:contributor

• Nancy M. Lorenzon, Ph.D.
• Joseph Angleson
• Daniel Linseman

• Calcium dysregulation
• Malignant hyperthermia
• Oxidative stress
• Purkinje cell
• Ryanodine receptor
• Biology
• Cell and Developmental Biology
• Life Sciences

Statement dc:rights

• <p>Copyright is held by the author. User is responsible for all copyright compliance.</p>

Language dc:language

en

Repository record dc:identifier

https://digitalcommons.du.edu/etd/574

OAI identifier oai:identifier

oai:digitalcommons.du.edu:etd-1573