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[Ganglionic-blockading action of bis-ammonium compounds]
Neirofiziologiia = Neurophysiology
|January 1, 1984
Summary
Bis-ammonium compounds block acetylcholine channels by binding to open channels. Their voltage-dependent binding kinetics influence ganglion-blocking activity, impacting nerve signal transmission.
Area of Science:
- Neuroscience
- Pharmacology
- Biophysics
Background:
- Acetylcholine receptors are crucial for nerve signal transmission.
- Bis-ammonium compounds are known to affect neuronal function.
- Understanding their mechanism is key to developing new therapeutics.
Purpose of the Study:
- To investigate the actions of bis-ammonium compounds on acetylcholine-activated channels.
- To elucidate the kinetics of compound binding and dissociation from open channels.
- To correlate these kinetics with the overall ganglion-blocking activity.
Main Methods:
- Utilized voltage-clamped neurons from rabbit superior cervical ganglion.
- Measured fast excitatory postsynaptic current decay to assess channel closure kinetics.
- Employed double-pulse acetylcholine application to determine compound dissociation kinetics.
Main Results:
- The rate constant of bis-ammonium compound binding to open channels increased with membrane hyperpolarization.
- The rate constant of compound dissociation decreased with membrane hyperpolarization.
- Voltage-dependence of binding increased with polymethylene chain length; nitrogen group radicals had no effect.
- In situ cat ganglion studies showed correlation between binding kinetics and blocking activity.
Conclusions:
- Ganglion-blocking actions of bis-ammonium compounds are primarily determined by their channel-blocking activities.
- Voltage-dependent binding kinetics play a significant role in their efficacy.
- Structural modifications (polymethylene chain length) can modulate this activity.