Amiridin and tacrine modulation of the activity and plasticity of the cholinoreceptors of neurons of the common snail: phenomenology and mechanisms.
The influence of amiridin and tacrine on the membrane potential, activity, and plasticity of cholinoreceptors was investigated using the methods of recording of intracellular potentials and transmembrane currents in identified RPa3 and LPa3 neurons of the common snail. Amiridin and tacrine (1-100 mumole/liter) do not exert appreciable influences on the membrane potential of the cells. Both compounds modulate the activity of cholinoreceptors, judging from their influence on the inward current induced by local application of the acetylcholine: the duration of the ACh current increases and its amplitude varies biphasically (a short-latency increase is succeeded by a decrease). Amiridin and tacrine intensify the extinction of the ACh current induced by repeated applications of ACh to the soma. The acetylcholinesterase inhibitor, physostigmine, exerts a similar modulatory influence on the ACh current and on its extinction, and also prevents the manifestation of the effects of amiridin and tacrine. Amiridin and physostigmine directly influence the cholinoreceptors and the ionic membrane channels controlled by them by similarly altering the voltage-current characteristics (VAC) of the ACh current, and by shifting the reversal potential of the ACh current in the negative direction, bringing it closer to the equilibrium potential for chloride ions; this may be interpreted as a result of the nonidentical action of these compounds on the various ionic currents controlled by cholinoreceptors. The hypothesis is advanced that the modulatory influence of amiridin, tacrine, and physostigmine on the activity and plasticity of the cholinoreceptors is governed by their direct membrane-cytoplasmic action.
Burov YuV
All-Union Scientific Center for the Safety of Biologically Active Substances, Staraya Kupavna. M.V. Lomonosov Moscow State University.
Drozdova
E I
EI
Pivovarov
A S
AS
Robakidze
T N
TN
D000109:Acetylcholine / Q000502:physiology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D002800:Cholinesterase Inhibitors; D006372:Helix, Snails / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology*
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D007473:Ion Channels; D011619:Psychotropic Drugs; D011950:Receptors, Cholinergic; D013619:Tacrine; C049860:amiridine; D000109:Acetylcholine