Development of postsynaptic function in muscle membrane

Dissertation (Ph.D.) University of Alaska Fairbanks, 1987The development of postsynaptic function in skeletal muscle of Xenopus laevis was studied in vivo in order to address the following questions: What changes take place in acetylcholine receptor (AChR) channel function during muscle development and when do they occur? Does muscle activity regulate the development of postsynaptic function? Do functionally different muscles have different programs of postsynaptic development? Single channel recordings from nonjunctional membrane revealed a class of low conductance (30 to 40 pS), long open time (2-3 ms) AChR channels which appeared on embryonic membrane within 21 h of fertilization. At 45 h of age, a second class of higher conductance (40 to 60 pS), brief open time ($<$1 ms) channels began to be expressed and over the course of 4 days became the most frequently observed channel type. Concurrently, the open time of the low conductance channel decreased by half during development. These data explain the developmental change in duration of synaptic currents previously observed in myotomal muscle, and they lay the foundation for further studies on the molecular mechanisms of AChR development. The effect of immobilization on the development of synaptic currents in myotomal muscle was investigated by allowing embryos to develop in a bath containing tetrodotoxin, which eliminated muscle activity during formation and maturation of the neuromuscular junction. In both control and tetrodotoxin-immobilized animals, synaptic current rise times and decays developed in an equivalent fashion, indicating that muscle activity is not required for normal development of AChR channel gating or acetylcholinesterase (AChE) deposition at the neuromuscular junction. The development of synaptic currents was compared in two functionally different muscles, the interhyoideus and the superior oblique. Each muscle has a characteristic program of synaptic current development during synaptogenesis and during metamorphosis. The contrasting development of synaptic currents from the two muscles can be explained by different programs of AChR and AChE development