Effects of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and barium ions on frog neuromuscular transmission.
1. By applying electrophysiological techniques such as frequency facilitation, tetanic run-down and depression, recovery from depression and post-tetanic potentiation (PTP) of the end-plate potential (EPP), the effects on frog neuromuscular transmission of 2-(4-phenylpiperidino)cyclohexanol (AH5183), a compound known to inhibit specifically the loading of newly synthesized acetylcholine (ACh) molecules into synaptic vesicles, and Ba2+, a selective activator of the augmentation phase of PTP, were investigated to elucidate whether these were related to ACh turnover. 2. Effects of AH5183 and Ba2+ ions were frequency dependent. At low frequency of stimulation, both agents showed essentially no effects on the EPPs recorded from Mg2+-blocked preparations. 3. AH5183 pivoted the log-linear frequency facilitation relation clockwise without altering the intercept on the ordinate, whereas Ba2+ ions did so counter-clockwise. As is the case with Ca2+ ions, Sr2+ ions shifted the relation upwards leaving its slope unaffected. 4. AH5183 selectively depressed the component of potentiation in PTP while the effect of Ba2+ ions was a specific increase in the augmentation phase of PTP. 5. Ba2+ ions increased the amplitude of EPPs in the late depressed phase during the tetanic run-down and depression experiment, but 4-aminopyridine and Ca2+ ions failed to do so. 6. AH5183 increased, Ba2+ ions reduced but Ca2+ ions did not change the constant of recovery from depression of the EPP measured on curarized preparations. 7. The present results suggested that mobilization of the ACh quanta readily available for release might be a common mechanism underlying both frequency facilitation and two components of PTP (augmentation and potentiation). The term 'frequency facilitation' would be more comprehensive if it were re-termed 'frequency augmentation' or 'frequency potentiation'.
Maeno
T
T
Department of Physiology, Shimane Medical University, Izumo, Japan.
Shibuya
Y
Y
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009045:Motor Endplate / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000502:physiology*; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines; D011898:Ranidae; D013324:Strontium / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D000631:Aminopyridines; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D001464:Barium; C006189:vesamicol; D015761:4-Aminopyridine; D008274:Magnesium; D010622:Phencyclidine; D002118:Calcium; D013324:Strontium