Premium
The influence of ouabain on twitch potentiation by anticholinesterases in the phrenic nerve‐diaphragm muscles of mice
Author(s) -
Nishimura Masakazu,
Ohtani Hiroya,
Yagasaki Osamu
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11798.x
Subject(s) - neostigmine , hexamethonium , ouabain , chemistry , atropine , long term potentiation , phrenic nerve , physostigmine , inhibitory postsynaptic potential , pharmacology , anesthesia , acetylcholine , endocrinology , medicine , biochemistry , sodium , receptor , respiratory system , organic chemistry
1 (+)‐Tubocurarine, hexamethonium, atropine, ouabain, and removal of potassium from the bathing medium were examined for their effects on indirectly evoked twitches (IT) of mouse phrenic nerve‐diaphragm muscles in the presence or absence of neostigmine. 2 Neostigmine increased the amplitude of IT. The twitch potentiation was reduced by (+)‐tubocurarine at low concentrations that had no inhibitory effect on normal IT. Hexamethonium (10–100 μ m ), but not atropine (0.1–1 μ m ), partially inhibited the twitch potentiation. Neither hexamethonium nor atropine had an inhibitory effect on IT in the absence of neostigmine. 3 Ouabain (5 μ m ) abolished the twitch potentiation by neostigmine while having no inhibitory effect on directly evoked twitches in the presence of neostigmine and (+)‐tubocurarine together. 4 The potentiating effect of neostigmine was less in a potassium‐free bathing solution. The inhibitory effect of ouabain disappeared in this solution. 5 Reinclusion of KCl at 2.5 mM restored both the potentiating effect of neostigmine and the antagonistic effect of ouabain. This reinclusion did not potentiate IT in the absence of neostigmine. 6 An interaction resembling that between ouabain and neostigmine was obtained between ouabain and physostigmine or paraoxon. 7 Both endplate potentials (e.p.ps) and miniature e.p.ps increased in terms of their amplitude and duration in the presence of neostigmine. Ouabain did not reduce the enhanced endplate responses. 8 These results indicate that the potentiation of IT by anticholinesterases may occur via nicotinic receptors which are sensitive to both (+)‐tubocurarine and hexamethonium, and that the interaction between anticholinesterases and ouabain depends on the presence of K + . It appears that the mechanisms of twitch potentiation are dependent on the ionic gradients maintained by Na + ‐K + ‐ATPase.