Membrane alterations in skeletal muscle fibers of dystrophic mice

Abstract

Skeletal muscle fibers from dystrophic mice and littermate controls (ReJ-129) were characterized electrically and then injected with an intracellular marker. In this way they could be identified for examination with an electron microscope to correlate the relative time course of electrical and ultrastructural alterations resulting from the dystrophic process. On the average, dystrophic muscle fibers displayed decreased membrane potentials (-59 +/- 1.2 vs -79 +/- 0.7 mV for normals), decreased specific membrane resistivity (517 +/- 27 vs 642 +/- 34 omega-cm2 for normals), and depressed action potential (AP) maximum rates of rise (+Vmax) (352 +/- 9 vs 417 +/- 9 V/s for normals) and amplitudes (92 +/- 1.2 vs 102 +/- 1.0 mV for normals) at an experimentally polarized membrane potential of -90 mV. Membrane resistivity and AP +Vmax were decreased even in those fibers from dystrophic muscles that displayed normal ultrastructure (classified visually and by ratio of sarcoplasmic reticulum to total cell volume). These findings support the membrane hypothesis of muscular dystrophy that membrane lesions are the primary lesion in the disease process.

6-Mercaptopurine Treatment Affects the Membrane Potentials of Rat Skeletal Muscle Fibers

“…The depolarization observed in 0.1 mM [K] o in muscles from both 6-MP-treated and control rats may be due: (a) to an inhibition of the electrogenic component of the Na-K pump; and (b) to a decrease in K~ permeability (PK). Our results show that, as previously reported (Sellin and Sperelakis, 1978;Kerr and Sperelakis, 1983) there is an inhibition of the Na-K pump in low [K] because no additional depolarization was seen after the administration of ouabain. Since the inhibition of the electrogenic component of the Na-K pump cannot account for the entire depolarization seen in low [K]o, the remainder may be due to a decrease in PK.…”

“…Therefore, this difference could not account for the large difference in Em. Sperelakis, 1983. Values given are the mean * SE for the number of fibers given in parentheses.…”

“…The similarities with genetic murine muscular dystrophy prompted us to investigate the electrophysiological abnormalities produced in the extensor digitorum longus (EDL) muscle of 6-MP-treated rats. The EDL, a mixed muscle histochemically but with all muscle fibers of the fast-twitch type (Close, 1967), is a well characterized muscle electrophysiologically, and it has been extensively studied in genetic murine muscular dystrophy (Harris, 1971; Harris and Marshall, 1973;Sellin and Sperelakis, 1978; Kerr and Sperelakis, 1983). METHODS Neonatal Sprague-Dawley rats were treated with 6-mercaptopurine (6-MP) (2 mg/ kg sc daily) from the 2nd to 22nd days of life.…”

Excitation contraction coupling in normal and mdx mice

“…19, 20 We show here that there is probably no difference in passive membrane properties between normal and regenerated fibers found in adult mdx mice (Table l), and thus the lack of dystrophin in these mdx muscles appears to have no effect on fiber passive electrical properties. Following the identification of dystrophin and reports of its localization to the triadic junction in adult rat and rabbit muscle, a role for dystrophin in EC coupling has been proposed (see introduction and Refs.…”

The different intracellular action potentials of fast and slow muscle fibres

“…When the distance between the stimulating and recording electrodes is smaller than 0.7 mm there is no normal action potential at the recording site (Kerr and Sperelakis 1983). lAP records reported in the literature have been made at (very) small distances from the stimulating electrode, sometimes even with this electrode itself.…”