Autoregulation of Neuromuscular Transmission by Nerve Terminals.
Abstract
The objective of this project has been to investigate three mechanisms through which acetylcholine (ACh) release may be modulated prejunctionally at the motor nerve terminal of skeletal muscle: 1) prejunctional cholinoceptor regulation of ACh release, 2) modulation of ACh release through preconditioning patterns of nerve stimulation, and 3) precursor control of ACh release. Neuromuscular transmission has been assessed in the vascular perfused rat phrenic nerve-hemidiaphragm preparation (VPRH) by measuring the release of ACh directly by radioenzymatic assay or by chemiluminescence assay, and indirectly by intracellular recordings and by force of contraction (FC) measurements. Additional experiments have been done on rat sciatic nerve in order to examine the axonal transport of nicotinic binding sites. The mouse hemidiaphragm preparation has been used to study antidromic activity (backfiring) in the phrenic nerve in the presence of an anticholinesterase agent. Suberyldicholine, a potent nicotinic receptor agonist, caused a significant decrease in stimulus-evoked ACh release from VPRH. The natural agonist, ACh, provoked frequency-dependent negative feedback on subsequent release when the neuromuscular junction concentrations of ACh were raised with neostigmine or other acetylcholinesterase (AChE) inhibitors. The cumulative results from the project support the hypothesis that the nerve terminal possesses local mechanism for modulating ACh release in response to changing physiological or pharmacological demands and in the presence of AChE inhibitors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1985
- Accession Number
- ADA193338
Entities
People
- George G. Bierkamper
Organizations
- University of Nevada, Reno School of Medicine