Effects of a monoclonal anti-acetylcholine receptor antibody on the avian end-plate.
1. The effects of anti-acetylcholine receptor (AChR) monoclonal antibodies (mAbs) 370 and 132A on miniature end-plate potentials (MEPPs) and end-plate currents (EPCs) in the posterior latissimus dorsi muscle of adult chickens were investigated. 2. After incubation of the electrophysiological preparation with mAb 370 (5-50 micrograms/ml), which blocks both agonist (carbamylcholine) and alpha-bungarotoxin (alpha-BTX) binding and induces a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), MEPP and EPC amplitudes were irreversibly reduced. 3. This effect was not associated with any significant change in the time constant describing EPC decay (tau EPC), current reversal potential, or the voltage dependence of tau EPC. The tau EPC at -80 mV was 5.9 +/- 0.6 ms before incubation with mAb 370 (50 micrograms/ml) and 6.0 +/- 0.9 ms afterwards. Current reversal potential was -3.9 +/- 0.4 mV before mAb incubation and -4.8 +/- 1.5 mV afterwards. The change in membrane potential required to produce an e-fold change in tau EPC was 128 +/- 2.3 mV before antibody incubation compared to 125 +/- 6.6 mV after incubation. 4. A second anti-AChR mAb, 132A (50 micrograms/ml), which is capable of inducing the classically described form of EAMG without blocking agonist or alpha-BTX binding, or inducing hyperacute EAMG, produced no significant change in MEPP amplitude, EPC amplitude, tau EPC or EPC reversal potentials. 5. The mAb 370 (50 micrograms/ml) induced a partially reversible decrease of the quantal content of the neurally evoked end-plate potential (EPP). This effect was not observed with mAb 132A, (+)tubocurarine (10(-7)-10(-5) g/ml) or an irrelevant anti-oestrogen receptor mAb. 6. These data suggest that the rapid onset of weakness observed in chicken hatchlings after the injection of mAb 370 (Gomez & Richman, 1983) can be attributed to a combined effect of a block of acetylcholine (ACh)-induced ion channel activity in the postsynaptic membrane and a reduction of the neurally evoked release of acetylcholine from the nerve terminal.
Maselli
R A
RA
Department of Neurology, University of Chicago, IL 60637.
Nelson
D J
DJ
Richman
D P
DP
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002645:Chickens; D003864:Depression, Chemical; D066298:In Vitro Techniques; D009045:Motor Endplate / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D011950:Receptors, Cholinergic; D014403:Tubocurarine