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Properties of junctional and extrajunctional acetylcholine‐receptor channels in organ cultured human muscle fibres
Author(s) -
CullCandy S. G.,
Miledi R.,
Uchitel O. D.
Publication year - 1982
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1982.sp014452
Subject(s) - acetylcholine receptor , chemistry , biophysics , conductance , neuromuscular junction , tendon , acetylcholine , anatomy , electrophysiology , receptor , biology , biochemistry , endocrinology , neuroscience , physics , condensed matter physics
1. Current noise, obtained during steady ionophoretic application of acetylcholine (ACh) to voltage‐clamped human fibres has been analysed to derive properties of end‐plate channels and also extrajunctional ACh‐activated channels which are present at the muscle—tendon junction of normal fibres. In addition, ACh‐receptor channels present at the end‐plate and tendon region in organ cultured muscles have been compared with those in fresh muscles. 2. Extrajunctional channels in the tendon region of fresh fibres have a longer mean life‐time, τ, and a smaller single channel conductance, γ, than the junctional channels. τ was 1·71 ±0·11 msec and γ was 25·05 ± 1·18 pS for junctional channels; τ was 3·16 ± 0·33 msec and γ was 12·76 ± 1·29 pS for extrajunctional channels. 3. Properties of channels in the end‐plate and tendon region were unchanged during short‐term (< 7 days) organ culture at 23 or 36 °C. The voltage sensitivity of the mean channel life‐time was similar at junctional and extrajunctional sites. 4. In muscles organ cultured for 7 days at 36 °C, double component noise spectra were obtained at some end‐plates. The fast and slow time constants underlying the noise appeared to correspond to simultaneous activation of junctional and extrajunctional channels. 5. After organ culture for 3‐4 weeks at 23 °C the mean life‐time of the end‐plate channels was prolonged while their single channel conductance was unchanged, τ = 3·58 ± 0·16 msec; γ = 22·11 ± 0·83 pS ( V m = ‐80 mV, T = 21 °C). 6. As end‐plate channel properties were unchanged in short‐term cultures it was possible to assess post‐junctional sensitivity by comparing miniature end‐plate current (m.e.p.c.) amplitudes in both normal and myasthenia gravis affected muscles. No evidence was found for a change in post‐synaptic sensitivity during organ culture at 23 °C of normal or myasthenia gravis muscle fibres, which seems to rule out reversible block of receptors by anti‐receptor antibody as playing an important role in myasthenia gravis.