Neurons perform complex computations, communications and precise
transmissions of information in the form of action potentials (APs). The high level of
heterogeneity and complexity at all levels of organization within a neuron and the
functional requirement of highly permeable cell membranes leave neurons exposed to
damage when energy levels are insufficient for the active maintenance of ionic gradients.
When energy is limiting the ionic gradient across a neuron’s cell membrane risks being
dissipated which can have dire consequences. Other researchers have advocated
“generalized channel arrest” and/or “spike arrest” as a means of reducing the neuronal
permeability allowing neurons to adjust the demands placed on their electrogenic pumps
to lower levels of energy supply. I investigated the consequences of hypoxia on the
propagation of a train of APs down the length of a fast conducting axon capable of
transmitting APs at very high frequencies. Under normoxic conditions I found that APs
show conduction velocities and instantaneous frequencies nearly double that of neurons
experiencing energy limiting hypoxic conditions. I show that hypoxia affects AP
conduction differently for different lengths of axon and for APs of different instantaneous
frequencies. Action potentials of high instantaneous frequency in branching lengths of
axon within ganglia were delayed more significantly than those in non-branching lengths
contained within the connective and fail preferentially in branching axon. I found that
octopamine attenuates the effects of hypoxia on AP propagation for the branching length
of axon but has no effect on the non-branching length of axon. Additionally, for
energetically stable cells, application of the anti-diabetic medication metformin or the
hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288
resulted in a reduced performance similar to that seen in neurons experiencing energetic
stress. Furthermore both metformin and ZD7288 affect the shape of individual APs
within an AP train as well as the original temporal sequence of the AP train, which
encodes behaviourally relevant information. I propose that the reduced performance
observed in an energetically compromised cell represents an adaptive mechanism
employed by neurons in order to maintain the integrity of their highly heterogeneous and
complex organization during periods of reduced energy supply. / Thesis (Master, Biology) -- Queen's University, 2011-10-07 14:41:46.972
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/6830 |
| Date | 07 October 2011 |
| Creators | SPROULE, MICHAEL |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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