A comparative electrophysiological study of motor end‐plate diseased skeletal muscle in the mouse.

Abstract

SUMMARY1. Experiments using intracellular recording, stimulation, and microionophoretic techniques were performed on extensor digitorum longus nerve-muscle preparations excised from mice having hereditary 'motor end-plate disease'. Control experiments were performed on normal innervated and chronically denervated nerve-muscle preparations.2. Two physiologically distinct groups of muscle fibres were found in the diseased muscles. Group I is similar to normal innervated muscle with respect to resting potentials, cable properties, neuromuscular transmission, miniature end-plate potentials, and extrajunctional acetylcholine sensitivity. Group II is similar to denervated muscle in the above respects except that (i) neuromuscular transmission, though abnormal, was present, and (ii) miniature end-plate potentials (m.e.p.p.s), often having large amplitudes, were found in these muscle fibres.3. Large m.e.p.p.s appear to be due to an increase in muscle fibre input resistance and to the quantal release of abnormally large amounts of acetylcholine from motor nerve terminals.4. Nerve stimulation of Group II muscle fibres evoked action potentials with a delayed repolarization phase, suggesting that a prolonged acetylcholine-induced conductance change occurs at motor end-plates.5. Neuromuscular physiology in motor end-plate disease is similar to that reported for frog nerve-muscle preparations which have been incubated in high Ca2+ Ringer.

Early Changes of Neuromuscular Transmission in the SOD1(G93A) Mice Model of ALS Start Long before Motor Symptoms Onset

“…Together, these events may cause an increase in cytoplasmic Ca 2+ levels thereby increasing the spontaneous synchronized release of acetylcholine. GMEPPs have also been reported to be enhanced under pathological conditions like paralysis [35], nerve terminal sprouting and synapse remodeling [36], nerve terminals in degeneration [37] and in several motor endplate diseases [38]. Thus, the results described here suggest that diaphragm muscle from SOD1(G93A) mice already presents morphological changes in the pre-symptomatic phase.…”

The giant miniature endplate potentials frequency is increased in aged rats

“…Taken together these events may cause an increase in cytoplasmatic Ca 2+ levels thereby increasing the spontaneous synchronized release of acetylcholine. Enhanced GMEPPs frequency has been reported to occur in different pathological conditions like paralysis [7], nerve terminal sprouting and synapse remodeling [20], nerve terminals in degeneration [10] and in motor endplate diseases [21] such as ALS [12]. Interestingly, some of these features have been described in aged neuromuscular junctions, namely decreased sprouting and increased number of nerve terminals per endplate [22,23], which are also associated to "constitutive secretion" [24].…”

Mutation Detection in the and Alleles of the Sodium Channel

“…Spontaneous endplate potentials have been recorded in nerve/muscle preparations from homozygous med mice, demonstrating that the components of the neurotransmitter release machinery in the presynaptic nerve terminal are functional (Duchen and Stefani, 1971;Angaut-Petit et al, 1982). The failure of transmission across the neuromuscular junction has been directly demonstrated by the lack of evoked potentials from muscle fibers of med mutants after electrical stimulation of the nerve (Duchen and Stefani, 1971;Harris and Ward, 1974;Weinstein, 1980).…”