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Permanent link (DOI): https://doi.org/10.7939/R3230H

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Development of the Voltage-Gated Sodium and Potassium Currents Underlying Excitability in Zebrafish Skeletal Muscle Open Access

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Other title
Subject/Keyword
voltage-gated ion channels
development
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Coutts, Christopher
Supervisor and department
Warren Gallin, Biological Sciences
Peter Nguyen, Physiology
Declan Ali, Biological Sciences
John Chang, Biological Sciences
Examining committee member and department
Peter Nguyen, Physiology
Mel Robertson, Biology, Queen’s University
Declan Ali, Biological Sciences
Greg Goss, Biological Sciences
Warren Gallin, Biological Sciences
John Chang, Biological Sciences
Department
Department of Biological Sciences
Specialization

Date accepted
2009-08-24T21:50:34Z
Graduation date
2009-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Excitable cells display dynamically regulated changes in the properties of ion currents during development. These changes are crucial for the proper maturation of cellular excitability, and therefore have the potential to affect more sophisticated functions, including neural circuits, movements, and behaviors. Zebrafish skeletal muscle is an excellent model for studying the development of ion channels and their contributions to excitability. They possess distinguishable populations of red and white muscle fibers, whose biological functions are well understood. The main objectives of this thesis were: (1) To characterize the development of muscle excitability by examining properties of voltage-gated sodium and potassium currents expressed in embryonic and larval zebrafish during the first week of development. (2) To elucidate some of the mechanisms by which ion current development might be controlled, beginning with activity-dependent and phosphorylation-dependent mechanisms. These objectives were approached using whole-cell electrophysiological techniques to examine the voltage-dependent and kinetic properties of voltage-gated sodium and potassium currents in intact zebrafish skeletal muscle preparations. Mutant sofa potato zebrafish, which lack functional nicotinic acetylcholine receptors, were then utilized to determine whether synaptic activity at the neuromuscular junction is required for proper ion current development. Finally, protein kinases were activated pharmacologically in order to determine whether they were able to modulate ion currents during development. The results revealed that properties of ion currents undergo a developmental progression, including increased current density, accelerated kinetics, and shifts in voltage-dependence; these developments correlated well with the maturation of muscle action potentials and the movements and behaviors they mediate. Sofa potato mutants were found to be deficient in certain aspects of ion current development, but other aspects appeared to be unaffected by a lack of synaptic activity. Protein kinase A demonstrated the ability to drastically reduce potassium current density; however the effects of PKA were similar at all developmental stages. Overall, these findings provide novel insight into the roles played by voltage-gated currents during the development of excitability in zebrafish skeletal muscle, and expand the rapidly growing body of knowledge about ion channel function in general.
Language
English
DOI
doi:10.7939/R3230H
Rights
License granted by Christopher Coutts (christopher.a.coutts@gmail.com) on 2009-08-24T11:55:05Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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