The Density of Acetylcholine Receptors and Their Sensitivity in the Postsynaptic Membrane of Muscle Endplates

Abstract

authors have requested readers to note that a p-D-glutamyl residue rather than the p-LIglutamyl residue, implied in the text, was used for the calculations. The conclusions drawn in the paper are correct, since the D and L configurations of the p-glutamyl residue adopt almost identical conformations in thyrotropin releasing factor (TRF). It is possible to use the results in Tables 2-4 of the original paper to obtain the lowenergy conformations of TRF by simply reversing the sign of {,. The conformations thus obtained will not be the exact energy minima, but will represent all of the low-energy conformations closely. In order to illustrate this point, the calculations of Table 2 in the original text (for "p-D-glutamyl" TRF) were repeated using a p-L-glutamyl residue, and the minimum-energy results are given below ( Table 1). The dihedral angles for all conformations are essentially the same except that the sign of {l is reversed. It should be noted that the N8 conformer of structure D is now only 0.1 kcal/mol higher in energy than conformer NE of structure A. The similarity of the "p-D-glutamyl" and "p-L-glutamyl" TRF conformations suggests that the former should be active as a thyrotropin releasing factor.

Properties of fibres, endplates and acetylcholine receptors in the diaphragm, masseter, laryngeal, abdominal and limb muscles in the goat

“…3s Another study in the mouse tbund that the number but not the density of receptors per endplate varied directly with fibre s.ize. 33 The present estimates of the mean number (8.0-14.5'x 106) anddensity (8.9-22.3 x 103 lam -2) of receptors per endplate in goat muscles appear less than or comparable to estimates for the rat sterriomastoideus (36-47 x 106), 36 cat popliteus and extensor digitorum Iongus (58 _+ 6 x 106), 34 frog cutaneous pectoris (26,000 jam -2 on the thickened postjunctional membrane), 37 or different muscles in the mouse (9.7-35..8 x 106 and 8,500--47,800 ~m-2). 12.20.33.38.39 It is not clear to what extent differences among species and methods contribute to these discrepancies, or to the marked variations in estimates of receptor number or density between available report s. t 2.20.33-39 in summary, this study has shown that in the goat fibre size increased and the ratio of the endplate area to fibre area decreased in the order laryngeal, diaphragm, masseter, then limb and abdominal muscles, but differences in fibre composition did not follow a similar systematic order between these five muscles groups, and endplate size, receptor number or receptor density did not differ significantly between these muscles.…”

A possible involvement of cyclic AMP in the expression of desensitization of the nicotinic acetylcholine receptor

“…It is also conceivable that a short bath incubation of the myoballs with forskolin prevents the accumulation of CAMP to a level which would phosphorylate the AChR leading to the appearance of signs characteristic of desensitization. Third, since forskolin (I-100 PM) did not induce voltage-and timedependent effects on the EPCs as seen with many other noncompetitive antagonists of the AChR such as phencyclidine, phenothiazines, meproadifen and histrionicotoxin [5,6,, the possibility of a blockade of AChR in the resting state seems unlikely. The possibility that the desensitization observed with forskolin could be due to continuous and excessive exposure to ACh because of a blockade of AChE by forskolin was also considered.…”

“…Denervation of the muscles 10 days prior to the day of experiment and measurement of junctional and extrajunctional ACh sensitivity to microiontophoretic application of ACh were performed according to [6,14,15]. Briefly, micropipettes filled with 3 M KC1 with a resistance of 15-25 MQ were used for recording ACh-induced potentials.…”

“…The AChR, upon binding of the agonist, can also undergo a slow transition to a refractory or desensitized state [l-5]. This condition, brought about by very high concentrations of the agonist, may not be evident under physiological conditions since the quantity of ACh released during repetitive nerve firing does not appear likely to be sufficient to induce desensitization [6]. However, desensitization of the AChR may serve as an autoregulatory function, protecting the junctional region against excessive depolarization.…”

Ultrastructural visualization of the transmembranous and cytomatrix-related part of nicotinic acetylcholine receptor of frog motor endplate by means of an immunochemical avidity of IgG for d-tubocurarine.

“…At the electron microscopic level, nAChR was localized by autoradiography using radioactive α-bungarotoxin [11][12][13][14][15][16][17] and by immunoperoxidase visualization of α-bungarotoxin bound to nAChR [18]. However, limited resolving power of autoradiography and diffusion of diaminobenzidine (DAB) precipitates in the synaptic cleft did not provide localization of nAChR at molecular level.…”