The Effects of 3,4-Diaminopyridine on Neurotransmitter Release in a Frog Model of Lambert-Eaton Myasthenic Syndrome

UNCP Author/Contributor (non-UNCP co-authors, if there are any, appear on document)
Adria Pontious (Creator)
The University of North Carolina at Pembroke (UNCP )
Web Site:
Robert E. Poage

Abstract: Lambert-Eaton Myasthenic Syndrome (LEMS) is a neuromuscular disorder characterized by muscle weakness in which the motor nerve has difficulty releasing enough neurotransmitter to cause muscle contraction. Through clinical trials, 3,4-Diaminpyridine (DAP) has been shown to successfully treat LEMS by increasing muscle contraction and strength. The precise effect of diaminopyridine on synaptic facilitation (an increase in transmitter release seen during high frequency stimulation) is not well understood. I order to study LEMS conditions, a well described neuromuscular synaptic preparation and a selective neurotoxin is used to model LEMS in an animal. Using the cutaneous pectoris muscle of the Rana pipiens (leopard frog), the electrical response of muscle cells to various frequencies of stimuli was measured using intracellular recording methods. The amplitude of the muscle cells response to the nerve stimuli was used as an assay of neurotransmitter release in both LEMS-like and control (low calcium) conditions. The data indicate that diaminopyridine increases the amount of neurotransmitter released in both control and LEMS conditions, but decreases the degree of facilitation in both conditions. The preliminary results are not sufficient to determine whether diaminopyridine causes a higher level of facilitation in LEMS conditions than in the control (low calcium) conditions. The collected data are a foundation for the continued studies on the mechanism of action of DAP, and the functional arrangement of synaptic proteins in a model synapse. Additionally, the establishment of a research laboratory in an undergraduate biology department where none had previously existed was an important accomplishment of this project.

Additional Information

Honors Project
Language: English
Date: 2005
Lambert-Eaton Myasthenic Syndrome, LEMS, Neurotransmitter, Diaminopyridine, Synaptic Facilitation,

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