Physostigmine modulation of acetylcholine currents in COS cells transfected with mouse muscle nicotinic receptor.
Physostigmine (Phy), a reversible inhibitor of acetylcholine (ACh) esterase (AChE), may also act as a low potency agonist and a modulator of the nicotinic receptor. The actions of Phy on mouse muscle nicotinic receptors in the COS-7 cell line were studied by the patch-clamp technique. Currents were recorded in the whole-cell mode 3-7 days after cell transfection by plasmids coding alphabetagammadelta combination of receptor subunits. The application of ACh to cells clamped at -10 mV produced inward currents which displayed desensitization. The application of Phy in concentrations up to 1 x 10(-3) M did not give reliable specific whole-cell membrane responses. The application of Phy in concentrations of 10(-6)-10(-4) M together with ACh modulated the amplitude; accelerated desensitization of currents induced by ACh and increased the final extent of desensitization in a concentration-dependent manner. This finding is in contrast to the suppression and slowing down of desensitization by Phy and 1-methyl-galanthamine observed in Torpedo receptors.
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague, Czech Republic.
Lucie
L
Svobodová
Jan
J
Krůsek
Tomás
T
Hendrych
Frantisek
F
Vyskocil
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005822:Genetic Vectors / Q000235:genetics; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010830:Physostigmine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D014162:Transfection
D002800:Cholinesterase Inhibitors; D007473:Ion Channels; D011978:Receptors, Nicotinic; D010830:Physostigmine; D000109:Acetylcholine