Contractile and EMG studies of murine myotonia (mto) and muscular dystrophy (dy/dy)

Abstract

This report focuses on the myotonic (mto) mouse, an autosomal recessive neuromuscular mutant first described in 1982. Studies in vivo confirmed the presence of hindlimb rigidity during walking and typical myotonic electromyographic (EMG) discharges that persisted after nerve transection and complete neuromuscular blockade. Studies of the contractility of mto muscles in vitro revealed reduced peak isometric tetanic tension and greatly prolonged relaxation times. Tubocurarine did not affect tension parameters, but did antagonize the delayed relaxation in vitro. On the basis of EMG studies alone this mutant can accurately be described as myotonic. Reduction of the contractile abnormalities by tubocurarine in vitro, however, poses further questions regarding the nature of the disorder. Although the more familiar dystrophic mouse (dy/dy) has been termed "myotonic" by some, the new mto mutant differs from it in all aspects examined.

A surface EMG multi-electrode technique for characterizing muscle activation patterns in mice during treadmill locomotion

“…Entrikin et al, 1987;Carter et al, 1992;Chandran et al, 1995;Kennel et al, 1996;Loscher et al, 1989;Lorenc-Koci and Wolfahrt, 1999;Zielasek et al, 2000;Jinnah and Hess, 2004;Jinnah et al, 2005). A precise characterization of the nature of the motor disorder is essential for comparisons to the human counterpart.…”

“…Whelan, 2003) that has proven useful for both diagnosis and measurement of certain motor disorders in mice. It has been successfully applied in models of motor neuron disease, neuropathy, and myopathy (Entrikin et al, 1987;Carter et al, 1992;Chandran et al, 1995;Kennel et al, 1996;Zielasek et al, 2000). For these disorders, single electrode recordings in restrained animals are usually sufficient to uncover the presence and severity of characteristic physiological 0165-0270/$ -see front matter © 2005 Elsevier B.V. All rights reserved.…”

Fatigue-inducing stimulation resolves myotonia in a drug-induced model

“…Humans with myotonia experience limb muscle stiffness which interferes particularly with the initiation of movements [3,20-22]. Involvement of respiratory muscles may lead to "breathing difficulties", dyspnea, sleep apnea, and daytime alveolar hypoventilation [23-26].…”

“…The extent of myotonia, however, dissipates with repetitive contractions, the so-called warm-up phenomenon [2-4,16,21]. This has been examined in the context of a short series of low intensity contractions reducing myotonia during subsequent low intensity contractions [7,16,20,27] rather than in the context of repetitive contractions of sufficient severity to produce fatigue, such as might occur during athletic activities. The general purpose of the present study was therefore to examine myotonia during fatigue-inducing stimulation.…”

The Effect of Dehydroepiandrosterone Sulfate (DHEAS) on Myotonia: Intracellular Studies

“…Paramyotonia congenita has a Na channel abnormality (7,8) and cold-induced myotonia occurs, but the incidence of this disorder is very rare. Since most of the myotonic patients that we see are either myotonic dystrophy, or myotonia congenita and the physiological basis for myotonia is Cl channel defect, we used the animal model, mto mice, whose Cl channel does not develop due to stop codon (9)(10)(11)(12)(13)(14). We investigated the effects of DHEAS on myotonia in mto mice to determine or not whether this medication has an appropriate effect to abolish myotonia and yet does not cause muscle weakness.…”