Sodium Channel and Sodium Pump in Normal and Pathological Muscles from Patients with Myotonic Muscular Dystrophy and Lower Motor Neuron Impairment

Abstract

A B S T R A C T Two sodium transport systems have been analyzed in this work: the voltage-sensitive sodium channel and the (Na+, K+) ATPase pump. The sodium channel has been studied using a tritiated derivative of tetrodotoxin; the sodium pump has been studied using tritiated ouabain. Properties of interaction of tritiated tetrodotoxin and of tritiated ouabain with their respective receptors were observed in normal human skeletal muscle and in muscles of patients with myotonic muscular dystrophy and with lower motor neuron impairment.Levels of sodium pump and of sodium channels were measured at different stages of membrane purification. Microsomal fractions of normal human muscle have maximal binding capacities for tetrodotoxin of 230 fmol/mg of protein and of 7.4 pmol/mg of protein for ouabain.Dissociation constant for the complexes formed by the tetrodotoxin derivative and by ouabain with their respective receptors were 0.52 nM and 0.55 ,uM, respectively.In muscles from patients with myotonic muscular dystrophy, the maximal binding capacity for tetrodotoxin, i.e., the number of Na+ channels was found to be very similar to that found for normal muscle.The maximal binding capacity for ouabain, i.e., the number of Na+ pumps was three-to sixfold lower than in normal muscle. Dissociation constants for the com-

Ion transport in human skeletal muscle cells: disturbances in myotonic dystrophy and Brody's disease

“…Patients 1-10 have (Desnuelle et aL 1982), a raised Na* conductance at been described before (Benders et aL 1994a). Pseudorest (Rüdel & Lehmann-Horn 1985), and an altered myotonia is the most important clinical feature.…”

Ca‐dependent slow action potentials in human skeletal muscle

“…Modification of membrane conductances have been observed in myotonic muscular dystrophy and in lower motor neuron disease in human muscles (Desnuelle et al, 1982) and also in dystrophic mice Sperelakis, 1983b, 1983~). The bee-venom apamin, a blocker of Ca-activated K channels (K(ca) channels), selectively binds to muscle membranes of patients with myotonic muscular dystrophy, whereas the toxin does not bind to normal muscles (Renaud et al, 1986).…”

Na+-K+Pump Regulation and Skeletal Muscle Contractility

“…In homogenates of skeletal muscle samples from patients with myotonic muscular dystrophy, the content of [ 3 H]ouabain binding sites was three-to sixfold lower than in control subjects (104). The reduced Na ϩ -K ϩ pump content may explain the observation that in patients with muscular dystrophy, the muscles show increased [Na ϩ ] i and depolarization (120,178).…”