Back to Search
Start Over
Prolongation of evoked and spontaneous synaptic currents at the neuromuscular junction after activity blockade is caused by the upregulation of fetal acetylcholine receptors
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(35)
- Publication Year :
- 2006
-
Abstract
- It has been shown previously in a number of systems that after an extended block of activity, synaptic strength is increased. We found that an extended block of synaptic activity at the mouse neuromuscular junction, using a tetrodotoxin cuffin vivo, increased synaptic strength by prolonging the evoked endplate current (EPC) decay. Prolongation of EPC decay was accompanied by only modest prolongation of spontaneous miniature EPC (MEPC) decay. Prolongation of EPC decay was reversed when quantal content was lowered by reducing extracellular calcium. These findings suggested that the cause of EPC prolongation was presynaptic in origin. However, when we acutely inhibited fetal-type acetylcholine receptors (AChRs) using a novel peptide toxin (αA-conotoxin OIVA[K15N]), prolongation of both EPC and MEPC decay were reversed. We also blocked synaptic activity in a mutant strain of mice in which persistent muscle activity prevents upregulation of fetal-type AChRs. In these mice, there was no prolongation of EPC decay. We conclude that upregulation of fetal-type AChRs after blocking synaptic activity causes modest prolongation of MEPC decay that is accompanied by much greater prolongation of EPC decay. This might occur if acetylcholine escapes from endplates and binds to extrajunctional fetal-type AChRs only during large, evoked EPCs. Our study is the first to demonstrate a functional role for upregulation of extrajunctional AChRs.
- Subjects :
- Neuromuscular Junction
Tetrodotoxin
Biology
Motor Endplate
Synaptic Transmission
Neuromuscular junction
chemistry.chemical_compound
Mice
Fetus
Downregulation and upregulation
medicine
Extracellular
Reaction Time
Animals
Receptors, Cholinergic
Neurotransmitter
Evoked Potentials
Acetylcholine receptor
General Neuroscience
Electric Conductivity
Extracellular Fluid
Articles
Cell biology
Up-Regulation
medicine.anatomical_structure
chemistry
embryonic structures
Synapses
cardiovascular system
Calcium
Neuroscience
Homeostasis
Acetylcholine
medicine.drug
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 26
- Issue :
- 35
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....1a857be8c4eeee72849ec23c44dc7756