title: Neuromuscular Transmission in experimental autoimmune myasthenia gravis (EAMG). Quantitative ionophoresis and current fluctuation analysis at normal and myasthenic rat end-plates.
abstract: Chronic experimental autoimmune myasthenia gravis (EAMG) was induced in rats by immunization with acetylcholine receptor (AChR) purified from the electroplax of Torpedo californica. 35--40 days after immunization, serum anti-AChR antibody titers were about 40 nM. At this stage, electrophysiology was performed on isolated M. omohyoideus muscle-preparations from myasthenic and from normal (control) rats. For the study of the equilibrium interaction between acetylcholine (ACh) and AChR, dose-response curves were obtained by quantitative ionophoretic application of ACh to voltage-clamped end-plates. Analysis of dose-response curves yielded the following parameters: maximum end-plate conductance per unit surface gmax (EAMG) = 10.3 +/- 1.1 nS/micrometer 2, gmax (normal) = 20.2 +/- 1.8 nS/micrometer 2; apparent dissociation constant K (EAMG) = 96 +/- 5 microM, K (normal) = 58 +/- 6 microM; Hill-coefficient nH (EAMG) = 2.3 +/- 0.1, nH (normal) = 2.3 +/- 0.1. Single channel properties were derived from an analysis of ACh-induced end-plate current noise: the mean single channel conductance was gamma (EAMG) = 20.1 +/- 2.2 pS, gamma (normal) = 27.6 +/- 1.8 pS and the mean channel life-time tau (EAMG) = 1.39 +/- 0.09 ms, tau (normal) = 1.32 +/- 0.08 ms (T = 22 degrees C). The electrophysiological data are interpreted as follows: (1) At myasthenic end-plates there is a 50--60% reduction of functioning AChR (decrease of gmax). A total number of about 2 x 10(6) (1 x 10(6)) channels per end-plate was calculated for control (myasthenic) rats. (2) The affinity of AChR for ACh is reduced and/or there is an impediment of the conformational change from the closed- to the open-channel configuration (increase of K). (3) Single channel properties are essentially unaffected.
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology; D004557:Electric Organ; D005260:Female; D005399:Fishes; D007478:Iontophoresis; D009045:Motor Endplate / Q000502:physiology*; D009157:Myasthenia Gravis / Q000139:chemically induced / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000502:physiology*; D051381:Rats; D011950:Receptors, Cholinergic / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D011950:Receptors, Cholinergic; D000109:Acetylcholine