Date of Award

1-1-2010

Document Type

Thesis

Degree Name

M.S.

Department

Biological Sciences

First Advisor

Nancy M. Lorenzon

Keywords

Calcium dysregulation, Malignant Hyperthermia, Oxidative stress, Purkinje cell, Ryanodine receptor

Abstract

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.

Provenance

Recieved from ProQuest

Rights holder

Jason Santiago

File size

59 p.

File format

application/pdf

Language

en

Discipline

Biology, Neurosciences, Cellular biology

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