Autoregulation of Neuromuscular Transmission by Nerve Terminals
Abstract
The objective of this project has been to investigate three prejunctional mechanisms that may modulate acetylcholine (ACh) release at the motor nerve terminal of skeletal muscle: 1) prejunctional nicotinic cholinoceptor regulation of release, 2) modulation through preconditioning patterns of nerve stimulation, and 3) precursor control. In addition, the influence of acetylcholinesterase (AChE) inhibition on these mechanisms has been examined. 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 chemiluminescent assay and indirectly by intracellular recordings and force of contraction measurements. Additional experiments have been done on rat sciatic nerve in order to examine the axonal transport of nicotinic binding sites. Pharmacologic experiments with several nicotinic agonists and antagonists indicate that motor nerve terminals are populated by nicotinic cholinoceptors which act to modulate the amount of ACh release. Receptor binding studies with Iodine 125-alpha bungarotoxin suggest that these nicotinic receptors resemble nicotinic receptors of the central nervous system. These receptors, are also responsible for stimulus-induced antidromic activity (backfiring) in the phrenic nerve. Studies with calcium channel blockers and calcium-calmodulin inhibitors suggest a central role for calcium in the phenomenon of backfiring. Evidence has also been obtained that choline availability can influence ACh release.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1985
- Accession Number
- ADA212096
Entities
People
- George G. Bierkamper
Organizations
- University of Nevada, Reno School of Medicine