Dimensions of the ion channel in neuronal nicotinic acetylcholine receptor as estimated from analysis of conformation-activity relationships of open-channel blocking drugs.
Relationship between the size of the molecule in the series of organic ions Et3+N--(CH2)5--+NR1R2R3 (Ri--alkyl or cycloalkyl substituents) and their abilities to block nicotinic acetylcholine receptors (AChRs) due to their open-channel blockade in the neurons of autonomic ganglia and in frog end-plate was analyzed. All low-energy equilibrium conformations of the drugs were calculated by the molecular mechanics method. A unique rectangular channel profile 6.1 x 8.3 A, for which the best correlation between blocking activity of the drugs and total population of their conformations being able to penetrate into the channel, was deduced from all those tested.
Zhorov
B S
BS
Pavlov Institute of Physiology, Leningrad, USSR.
Brovtsyna
N B
NB
Gmiro
V E
VE
Lukomskaya NYa
Serdyuk
S E
SE
Potapyeva
N N
NN
Magazanik
L G
LG
Kurenniy
D E
DE
Skok
V I
VI
D000818:Animals; D001665:Binding Sites; D002412:Cations; D002415:Cats; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008968:Molecular Conformation; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002412:Cations; D007473:Ion Channels; D011978:Receptors, Nicotinic