Author/Editor		Zorec, Robert; Scuka, Maria; Kordaš, Marjan
Title		Effects of irreversible and reversible cholinesterase inhibitors on single acetylcholine-activated channels
Type		članek
Source		J Membr Biol
Vol. and No.		Letnik 125, št. 1
Publication year		1992
Volume		str. 41-8
Language		eng
Abstract		The use of cholinesterase (CHE) inhibitors provided valuable information about the mechanism(s) of neuromuscular transmission, but questions on side effects at the level of AChactivated channels were raised. Patch-clamp recording was used to study the effects of prostigmine (PST) and methanesulfonyl fluoride (MSF), a reversible and an irreversible cholinesterase inhibitor, respectively, on ACh-activated channels. We found that these drugs diminish the average dwell time of elementary currents from around 5 msec (control) to less than 1 msec in the presence of PST (20 micro M) or MSF (5 mM) (at room temperature). With MSF the ACh-activated channel conductance of the most frequently observed amplitude class decreased from 45 pS (control) to 30 p S, but not in the presence of PST. In control conditions there were also amplitude classes of60 and 24 pS, with probabilities ofoccurrence less th. 10 per cent . In the presence of 1.5 mm MSF, where current dwell time was not affected, additional subconductance states of 19 and 36 pS were observed and may be due to partial blockade ofthe open channel. We conclude that the drug ofchoice to be used in studies on the role of CHE in the neuromuscular transmission is MSF, because at 20 micro M PST, where blockade of ACh-activated channels is significant, cholinesterase was reported to be partially inhibited, whereas at 1 mM MSF it is fully inhibited and the dwell time of ACh-activated channels is not affected.
Descriptors		CHOLINESTERASE INHIBITORS ACETYLCHOLINE ION CHANNELS MUSCLES ACETYLCHOLINE CELLS, CULTURED ELECTRIC CONDUCTIVITY ION CHANNELS MUSCLES RATS RATS, INBRED STRAINS RECEPTORS, CHOLINERGIC SULFONES