Meproadifen enhances activation and desensitization of the acetylcholine receptor-ionic channel complex (AChR): single channel studies.
The effects of the quaternary agent meproadifen on ACh-activated channel currents were studied on myoballs cultured from hind limb muscles of neonatal rats. Meproadifen (0.02-0.1 microM) combined with ACh (0.1-0.3 microM) in the patch pipette caused an increase, followed by a decrease, in the frequency of channel openings. At concentrations greater than 0.2 microM the initial phase was not detected and a rapid and marked reduction in the opening frequency was observed. Meproadifen (up to 2.5 microM) produced no change in the duration or conductance of the open state of ACh-activated channels. In addition, this agent induced the appearance of events with a marked increase in the 'noise' during the opening phase. The lack of effect under inside-out patch conditions suggested that meproadifen binds to a site located at the external portion of the nicotinic macromolecule and has no access to it through the cell membrane. This study indicated that non-competitive antagonists such as meproadifen can facilitate receptor activation and desensitization.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000502:physiology; D011335:Proadifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D011950:Receptors, Cholinergic; C019001:meproadifen; D011335:Proadifen; D000109:Acetylcholine