Postsynaptic potentiation and desensitization in frog neuromuscular junction.
The fractional increase in ACh responses that occurs at the beginning of each train of iontophoretically applied ACh pulses has been examined at the frog neuromuscular junction at room temperature, in the presence of active cholinesterase, during desensitization produced by a rapid sequence (every 20 s) of short (5 Hz, 5 s) iontophoretic trains of ACh. The fractional increase in ACh responses, which is used as an indicator of postsynaptic potentiation, becomes progressively greater with ACh application, often markedly (greater than 100%), although ACh responses are greatly reduced (as much as 90%) owing to desensitization. Clearly postsynaptic potentiation can exist concomitantly with desensitization. In addition, the dose-response curve is shifted to the right and its maximal response is diminished. The shift in the dose-response curve to the right, which can explain greater postsynaptic potentiation, is unlikely to be caused by accumulation of "monoligand-bound ACh receptor complexes," since experiments were done with active cholinesterase. The shift probably results from a greater number of desensitized receptors which, because of their large affinity for ACh molecules, serve as "high affinity traps." A small decrease of the maximal dose-response suggests only a small fractional decrease in the number of activable receptors, whereas a large shift to the right indicates a large fractional increase in the number of desensitized receptors. It appears that prior to ACh application only a small fraction of all receptors are desensitized. Alternatively, the shift to the right occurs because the cooperative action of ACh on receptors increases during desensitization.
Glavinović
M I
MI
Department of Anaesthesia Research, McGill University, Montréal, Qué., Canada.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D009469:Neuromuscular Junction / Q000502:physiology*; D011894:Rana pipiens
D000109:Acetylcholine