Properties of end-plate channels in rats immunized against acetylcholine receptors

1. Rats injected with purified acetylcholine receptors (AChR) extracted from electric organs of Torpedo marmorata showed clinical symptoms consistent with the development of experimental myasthenia gravis.2. Sera of rats with this disease contain high levels of anti-AChR antibodies. However, no simple correlation was found between antibody titre and miniature end-plate current (m.e.p.c.) amplitude.3. M.e.p.c.s. at the end-plates of rats injected with AChR (Anti-R), emulsified in complete Freund Adjuvant (CFA), were reduced to about one third the size of controls taken from rats injected only with CFA (Anti-CFA). Mean m.e.p.c. (Anti-R) = 0.73 +/- 0.06 nA; mean m.e.p.c. (Anti-CFA) = 2.43 +/- 0.12 nA (V(m) = -80 mV, T = 20 degrees C).4. The m.e.p.c. decay time constant, tau(m.e.p.c.), is similar at immunized and control rat end-plates. tau(m.e.p.c.) (Anti-R) = 1.32 +/- 0.06 msec; tau(m.e.p.c.) (Anti-CFA) = 1.31 +/- 0.06 msec (V(m) = -80 mV, T = 20 degrees C).5. The end-plate current decay time constant, tau(e.p.c.), is similar at immunized and control end-plates and in both cases depends exponentially on membrane potential. The change in membrane potential required to produce an e-fold change in tau(e.p.c.) is 102.0 +/- 5.72 mV at immunized (Anti-R) end-plates and 92.3 +/- 6.14 mV at control (Anti-CFA) end-plates at T = 10 degrees C.6. Acetylcholine noise was examined at immunized and control rat end-plates at 10 degrees C. Analysis of noise indicates that the single channel conductance, gamma, and mean channel life-time, tau(noise), are essentially unchanged by immunization against AChR. gamma (Anti-R) = 13.15 +/- 0.53 pS; gamma (Anti-CFA) = 12.50 +/- 0.50 pS; tau(noise) (Anti-R) = 2.9 +/- 0.18 msec; tau(noise) (Anti-CFA) = 2.68 +/- 0.14 msec (V(m) = -80 mV, T = 10 degrees C).7. Mean quantal content and Ca(2+) dependence of the end-plate potential are unchanged at immunized end-plates.8. It is concluded that at immunized end-plates the number of activated receptor-channel complexes is reduced without modification of single channel properties. In this respect the immunized rat end-plate is a good model for myasthenia gravis affected human end-plates.