Open channel and competitive block of nicotinic receptors by pancuronium and atracurium.
Mouse myotubes were used to investigate effects of the nondepolarizing neuromuscular blocking drugs pancuronium and atracurium on embryonic-type nicotinic acetylcholine receptor channels. Experiments were performed using patch-clamp techniques in combination with devices for ultra-fast solution exchange at outside--out patches. Application of 0.1 mM acetylcholine resulted in a fast current transient. When the peak amplitude was achieved, the current decayed monoexponentially due to desensitization. After application of drugs (pancuronium or atracurium), two different mechanisms of block were observed: (1) open channel block of embryonic-type nicotinic acetylcholine receptor channels after coapplication of blocker and acetylcholine, characterized by decrease of the time constant of current decay; (2) competitive block of embryonic-type nicotinic acetylcholine receptor channels by pancuronium or atracurium after preincubation of outside-out patches with the respective blocker. Different affinities of pancuronium (K(B) approximately 0.01 microM) and atracurium (K(B) approximately 1 microM) to embryonic-type nicotinic acetylcholine receptor channels were observed.
Löwenick
C V
CV
Department for Anesthesiology of the Technical University Munich, Ismaninger Str. 10, 81675 München, Germany.
Krampfl
K
K
Schneck
H
H
Kochs
E
E
Bufler
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001279:Atracurium / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D004553:Electric Conductivity; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010197:Pancuronium / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D003473:Neuromuscular Nondepolarizing Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D001279:Atracurium; D010197:Pancuronium; D000109:Acetylcholine