Year of Publication

2008

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Arts and Sciences

Department

Biology

First Advisor

Dr. Robin Lewis Cooper

Abstract

Intracellular Ca2+ ions are highly regulated in animal cells for them to function normally. Since the tight regulation of [Ca2+]i is so ubiquitous among cells, it is not surprising that altered function in [Ca2+]i regulation is associated with a myriad of disease states in humans. This is particularly evident in pacing myocytes and nerve terminals related to synaptic transmission. A common thread through this dissertation is on the role of three regulators proteins that are common to many cell types. These are the plasmalemmal Na+/Ca2+ exchanger (NCX), the Ca2+-ATPase (PMCA) and the SERCA on the endoplasmic reticulum. In chapter 1 a historical overview is provided on how the understanding in the importance of Ca2+ came about. In Chapter 2, I address indirectly the function of residual [Ca2+]i on the efficacy of synaptic transmission by quantal analysis but also develop novel means of assessing quantal analysis to assign a n and p value to particular synapses. Chapters 3 and 4 address the role of the three Ca2+ regulator proteins in short bursts of synaptic transmission related to short-term facilitation or depression depending on the type of neuromuscular junction (NMJ). Two key model NMJs I used were the crayfish (Chapter 3) and the larval Drosophila (Chapter 4). For comparative purposes in investigating the role of the three proteins in [Ca2+]i regulation, I used the Drosophila larval heart preparation (Chapter 5). Throughout these studies, I used various pharmacological and ionic approaches to compromise the function of these Ca2+ channels. The results were unexpected in some cases due to non-specific effects of the pharmacological agent or ionic manipulations. In addition, a mutational line of Drosophila was used to asses SERCA function, but the results at the NMJ were not as expected. However, results with the mutation on the function of the heart were promising. The significance of these studies stresses that multiple approaches to compromise channels is warranted and the findings should be beneficial for future investigators to advance in mechanistic studies.

Included in

Biology Commons

Share

COinS