Altered developmental changes of neuromuscular junction in hypo‐ and hyperthyroid rats

Abstract

SUMMARY1. Effects of thyroid hormone on the development of neuromuscular junctions (n.m.j.s.) were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo-and hyperthyroid rats from the age of birth (day 0) to day 35.2. Hypothyroidism in new-born rats was induced either by daily administration of propylthiouracil to mothers or by subcutaneous injection of 150 1sCi l311 on day 1. Hyperthyroidism was induced by daily injection of thyroxine.3. In normal rats up to day 10, muscle fibres were innervated polyneuronally. By day 20, multiple innervation was eliminated and muscle fibres received only a single input. In hypothyroid rats elimination of polyneuronal innervation was retarded by 5-8 days, while in hyperthyroid rats the elimination was accelerated by 2-3 days.4. The frequency of miniature end-plate potentials (m.e.p.p.s) in normal rats increased from one per 40 sec on days 0-5 to 1/sec on days 25-35. The m.e.p.p. frequency in hypothyroid rats was 25-65 % of that in normal rats of the same age.In hyperthyroid rats the m.e.p.p. frequency was normal up to day 18 but subnormal afterwards. The duration ofm.e.p.p. measured on day 22-23 was slower in hypothyroid rats and faster in hyperthyroid rats, relative to m.e.p.ps in normal rats.5. The sensitivity to acetylcholine (ACh) at extrajunctional regions in normal rats was about 100 mV/nC at birth and declined to 1 mV/nC by day 26. In hypothyroid rats, the ACh sensitivity was as high as 30 mV/nC on day 26; in hyperthyroid rats, ACh sensitivity on day 26 was undetectable.6. With pairs of nerve stimuli (applied at a 50 msec interval), the second end-plate potential was facilitated until day 10 and depressed after day 16 in normal rats. This shift from facilitation to depression during development was not altered in either hypoor hyperthyroid rats.7. It is concluded that the lack and excess of thyroid hormone retards and facilitates the development of n.m.j.s. respectively. Possible mechanisms for this altered development are discussed.

Nerve-dependent modulation of acetylcholine receptor epsilon-subunit gene expression

“…By day 12-l 5, y-mRNA is no longer detectable, whereas +mRNA is expressed at a maximum level. Consistent with results of earlier electrophysiological studies on the role of thyroid hormones in the maturation of the neuromuscular junction in newborn rats (Kawa and Obata, 1982), we found that thyroid hormones accelerated the switch from yto t-subunit mRNA. However, neither the dramatic postnatal rise in e-mRNA nor its sensitivity to thyroid hormones were observed in denervated newborn animals, suggesting that c-mRNA modulation is mediated by the motor nerve.…”

“…The similarity between the time-course of development of c-mRNA and the serum levels of thyroxine prompted us to study the role of thyroid hormones in the regulation of the switch from y-to r-subunit expression. Also in support of this hypothesis, Kawa and Obata (1982) For the purpose of assessing the role of thyroid hormone, mice were made hypothyroid by administration of PTU or hyperthyroid with thyroxine (see Materials and Methods). Figure 4 shows that in PTU-treated animals, serum thyroxine was below detectable levels.…”

The open duration of fetal ACh receptor‐channel changes during mouse muscle development

“…Newborn mice were made hypothyroid by feeding pregnant females from E14 with low‐iodine Remington's diet (Mucedola, Italy) and adding 0.1 % propylthiouracil (Sigma) to their drinking water, as described by Martinou & Merlie (1991). Hypothyroid mice were markedly smaller than controls, as expected (Kawa & Obata, 1982).…”

“…In hypothyroid mice, the increase in channel duration took place during the first postnatal week. This observation emphasizes the developmental significance of τ op lengthening, as in hypothyroid rats the maturation of the neuromuscular junction is comparably retarded (Kawa & Obata, 1982), and the γ subunit is still present in hypothyroid mice at P20 (Martinou & Merlie, 1991).…”

On the two subdivisions and intrinsic synaptic connexions in the submandibular ganglion of the rat.

“…Instruments). When necessary, high-gain d.c. recordings were displayed with an automatic d.c.-level compensation circuit (Kawa & Obata, 1982). To measure the membrane input resistances ofneurones, small hyperpolarizing currents (0 1-0-2 nA) were injected through the recording electrode.…”