Reliability of muscle fiber conduction velocity in the tibialis anterior

This document could not have been completed without the hard work of a number of individuals. First and foremost, my supervisor, Dr. David Gabriel deserves the utmost recognition for the immense effort and time spent guiding the production of this document through the various stages of completion. Also, aiding in the data collection, technical support, and general thought processing were Lab Technician Greig Inglis and fellow members of the Electromyographic Kinesiology Laboratory Jon Howard, Sean Lenhardt, Lara Robbins, and Corrine Davies-Schinkel. The input of Drs. Ted Clancy, Phil Sullivan and external examiner Dr. Anita Christie, all members ofthe assessment committee, was incredibly important and vital to the completion of this work. Their expertise provided a strong source of knowledge and went to ensure that this project was completed at exemplary level. There were a number of other individuals who were an immense help in getting this project off the ground and completed. The donation of their time and efforts was very generous and much needed in order to fulfill the requirements needed for completion of this study. Finally, I cannot exclude the contributions of my family throughout this project especially that of my parents whose support never wavers.

Cholesterol-Independent Effects of Methyl-b- Cyclodextrin on Chemical Synapses

The cholesterol chelating agent, methyl-b-cyclodextrin (MbCD), alters synaptic function in many systems. At crayfish neuromuscular junctions, MbCD is reported to reduce excitatory junctional potentials (EJPs) by impairing impulse propagation to synaptic terminals, and to have no postsynaptic effects. We examined the degree to which physiological effects of MbCD correlate with its ability to reduce cholesterol, and used thermal acclimatization as an alternative method to modify cholesterol levels. MbCD impaired impulse propagation and decreased EJP amplitude by 40% (P,0.05) in preparations from crayfish acclimatized to 14uC but not from those acclimatized to 21uC. The reduction in EJP amplitude in the cold-acclimatized group was associated with a 49% reduction in quantal content (P,0.05). MbCD had no effect on input resistance in muscle fibers but decreased sensitivity to the neurotransmitter L-glutamate in both warm- and coldacclimatized groups. This effect was less pronounced and reversible in the warm-acclimatized group (90% reduction in cold, P,0.05; 50% reduction in warm, P,0.05). MbCD reduced cholesterol in isolated nerve and muscle from cold- and warmacclimatized groups by comparable amounts (nerve: 29% cold, 25% warm; muscle: 20% cold, 18% warm; P,0.05). This effect was reversed by cholesterol loading, but only in the warm-acclimatized group. Thus, effects of MbCD on glutamatesensitivity correlated with its ability to reduce cholesterol, but effects on impulse propagation and resulting EJP amplitude did not. Our results indicate that MbCD can affect both presynaptic and postsynaptic properties, and that some effects of MbCD are unrelated to cholesterol chelation.