Pharmacological properties of nicotinic acetylcholine receptors in isolated Locusta migratoria neurones.
Mechanically dissociated neuronal cell bodies from the thoracic ganglia of Locusta migratoria were viable in culture conditions for up to 2 days and were voltage-clamped to record the effects of GABAergic drugs and physostigmine on the membrane conductance and ACh responses of the dissociated cells. Bicuculline, hydrastine, and gabazine inhibited the EC50 ACh responses of the cells. Both bicuculline and hydrastine were full inhibitors of the ACh responses but gabazine behaved as a partial inhibitor. Bicuculline, hydrastine, and gabazine inhibited the ACh responses in a non-competitive and voltage-independent fashion, suggesting that they are allosteric inhibitors of locust nicotinic ACh receptors. Physostigmine activated currents when applied onto isolated locust neurones. The responses activated by physostigmine were inhibited competitively by tubocurarine, which indicates that physostigmine interacts with the ACh site of locust nicotinic ACh receptors. However, maximal concentrations of physostigmine elicited currents of smaller amplitudes to those evoked by maximal ACh concentrations. Single-channel recordings suggest that the partial efficacy of physostigmine may reflect the low frequency of opening of physostigmine-induced single currents relative to that of ACh-single currents.
Jackson
Charles
C
School of Biological and Molecular Sciences, Oxford Brookes University, Oxford OX3 0BP, United Kingdom.
Bermudez
Isabel
I
Beadle
David J
DJ
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines; D001640:Bicuculline / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D006110:Grasshoppers / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D000470:Alkaloids; D044182:Benzylisoquinolines; D002800:Cholinesterase Inhibitors; D018756:GABA Antagonists; D011978:Receptors, Nicotinic; C013024:hydrastine; D010830:Physostigmine; D000109:Acetylcholine; D001640:Bicuculline