Myasthenia in frogs immunized against cholinergic-receptor protein.
Frogs immunized with cholinergic-receptor protein developed myasthenia in 116--175 days. The muscular weakness was overcome by subcutaneous administration of 20 microgram of neostigmine. Electromyograms showed a decline in action potential amplitude during a 2-Hz train. Nerve stimulation evoked subthreshold end-plate potentials (EPPs) averaging 10.4 +/- 7.4 mV, but at many junctions no EPP was obtained. Miniature EPP amplitude had a modal value of 0.15 mV compared with 0.35 mV for the controls. The corresponding means were 0.24 +/- 0.23 mV and 0.48 +/- 0.23 mV. Microperfusion with edrophonium (5 mg/l) increased the amplitude of EPPs and miniature end-plate potentials (MEPPS). Postjunctional response tested with 20 muM carbamylcholine was 56% of control. Postjunctional response by carbamylcholine iontophoresis gave 19 +/- 22 mV/nC compared with 76 +/- 50 mV/nC for the controls. The data indicate that the neuromuscular transmission deficits in receptor-immunized frogs are mainly postsynaptic in origin, but there may be additional presynaptic contributions. This amphibian model of myasthenia gravis offers many opportunities and advantages in the study of receptor-immunized animals.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001001:Anura; D004195:Disease Models, Animal; D004491:Edrophonium / Q000494:pharmacology; D007114:Immunization; D009123:Muscle Hypotonia; D009157:Myasthenia Gravis / Q000503:physiopathology*; D009388:Neostigmine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000503:physiopathology*; D011894:Rana pipiens; D011950:Receptors, Cholinergic / Q000276:immunology; D009435:Synaptic Transmission / Q000187:drug effects
D011950:Receptors, Cholinergic; D009388:Neostigmine; D004491:Edrophonium