Dynamics of fast synaptic excitation during trains of stimulation in myenteric neurons of guinea-pig ileum.
Fast excitatory postsynaptic potentials (fEPSPs) occur in bursts in the myenteric plexus during evoked motor reflexes in the guinea-pig ileum in vitro. This study used electrophysiological methods to study fEPSPs during stimulus trains to mimic bursts of synaptic activity in vitro. The amplitude of fEPSPs or fast excitatory postsynaptic currents (EPSCs) declined (rundown) during stimulus trains at frequencies of 0.5, 5, 10 and 20 Hz. At 0.5 Hz, fEPSP or fEPSC amplitude declined by 50% after the first stimulus but remained constant for the remainder of the train. At 5, 10 and 20 Hz, synaptic responses ran down completely with time constants of 0.35, 0.21 and 0.11 s, respectively. Recovery from rundown occurred with a time constant of 7 s. Mecamylamine, a nicotinic cholinergic receptor antagonist, or PPADS, a P2X receptor antagonist, reduced fEPSP amplitude, but they had no effect on rundown. Responses caused by trains of ionophoretically applied ATP or ACh (to mimic fEPSPs) did not rundown. Blockade of presynaptic inhibitory muscarinic, adenosine A1, opioid, alpha2-adrenergic and 5-HT1A receptors or pertussis toxin (PTX) treatment did not alter rundown. Antidromic action potentials followed a 10-Hz stimulus train. Iberiotoxin (100 nM), a blocker of large conductance calcium activated K+ (BK) channels, did not alter rundown. These data suggest that synaptic rundown is not due to: (a) action potential failure; (b) nicotinic or P2X receptor desensitization; (c) presynaptic inhibition mediated by pertussis-toxin sensitive G-proteins, or (d) BK channel activation. Synaptic rundown is likely due to depletion of a readily releasable pool (RRP) of neurotransmitter.
Ren
Jianhua
J
The Neuroscience Program and the Department of Pharmacology and Toxicology, Life Science B308, Michigan State University, East Lansing, MI 48824, United States. renjianh@msu.edu
Galligan
James J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D058916:Adenosine A1 Receptor Antagonists; D000255:Adenosine Triphosphate / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004964:Estriol / Q000031:analogs & derivatives* / Q000502:physiology* / Q000528:radiation effects; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology* / Q000528:radiation effects; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D019329:Idazoxan / Q000494:pharmacology; D007082:Ileum; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009197:Myenteric Plexus / Q000166:cytology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D000109:Acetylcholine; D058916:Adenosine A1 Receptor Antagonists; D000255:Adenosine Triphosphate; D058669:Adrenergic alpha-2 Receptor Antagonists; D004964:Estriol; D018756:GABA Antagonists; D019329:Idazoxan; D008464:Mecamylamine; D009270:Naloxone; D009292:Narcotic Antagonists; D018733:Nicotinic Antagonists; D010455:Peptides; D010852:Picrotoxin; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D011732:Pyridoxal Phosphate; D058829:Serotonin 5-HT1 Receptor Antagonists; D013806:Theophylline; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C053907:8-cyclopentyl-1,3-dimethylxanthine; C064719:iberiotoxin; C009341:estriol succinate