Action of antibodies directed against the acetylcholine receptor on channel function at mouse and rat motor end-plates.
1. The acute effects of antibodies (both polyclonal and monoclonal) raised against the acetylcholine receptor were studied at mouse and rat end-plates. Isolated muscles were incubated in solutions containing antibody for 2 1/4 to 3 1/2 h. Intracellular microelectrode techniques were then used to record miniature end-plate potentials (MEPPs) and voltage noise. 2. Most antibody preparations investigated did not reduce MEPP amplitudes as compared with controls. One monoclonal (C7) and one polyclonal (J) preparation irreversibly reduced MEPP amplitudes. Both preparations caused reductions in acetylcholine-induced depolarization and associated channel opening frequency (from voltage noise analysis). Single-channel depolarization was not altered by these antibodies. 3. On the basis of these and previous results, four antibody binding regions on the receptor surface were distinguished according to whether channel function and/or alpha-bungarotoxin binding were affected. Although most antibody preparations did not affect channel function, monoclonal antibody C7 appeared to alter function by acting on the channel itself so as to prevent channel opening.
Dolly
J O
JO
Department of Pharmacology, Royal Free Hospital School of Medicine, London.
Gwilt
M
M
Lacey
G
G
Newsom-Davis
J
J
Vincent
A
A
Whiting
P
P
Wray
D W
DW
D000818:Animals; D000906:Antibodies; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D009045:Motor Endplate / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*
D000906:Antibodies; D007473:Ion Channels; D011950:Receptors, Cholinergic