Sodium channel distribution in normal and denervated rodent and snake skeletal muscle.

Abstract

SUMMARY1. Sodium channel current density was measured using the loose-patch voltage clamp technique. Innervated rat, mouse and snake muscle had the highest density of Na+ channels in the end-plate region. These high Na+ channel densities were maintained in denervated muscle.2. Perijunctional membrane had a Na+ current density 5-to 10-fold greater than the density several hundred micrometres from the end-plate. In all muscles this concentration of channels near the end-plate persisted following denervation.3. At the tendon Na+ current density fell to low values (-1 mA/cm2). The decrease in density began about 300-500 ,m from the tendon. This pattern was found in all snake twitch fibres and fast-twitch (EDL) rat and mouse muscle fibres. This reduction in channel density near the tendon was not affected by denervation.4. Sodium channels in all regions of innervated rat and snake muscle fibres were highly sensitive to tetrodotoxin (TTX). Sodium channels in snake muscle remained sensitive to TTX after denervation. Sodium channels that are relatively resistant to TTX appeared in rat muscle after denervation. TTX-resistant channels were even more concentrated near the end-plate than were TTX-sensitive channels in innervated muscle. At the tendon TTX-resistant Na+ channel density decreased.5. We conclude that although the nerve presumably directs the localization of Na+ channels during development, the ability to maintain this distribution and to control the distribution of newly appearing channels persists long after the nerve has been removed.

Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using 125I-alpha scorpion toxin. II. Sodium distribution on postsynaptic membranes

“…However, no subtype difference between the synaptic-perisynaptic zone and the rest of the surface has been reported. It should also be noted that the distribution described here is roughly in accord with previous immunocytochemical localizations (Haimovich et al, 1987;Flucher and Daniel& 1989), the distribution of PScTx-binding sites at light microscopic level (Le Treut et al, 1990), and the perisynaptic Na+ current high density (Beam et al, 1985;Caldwell et al, 1986;Caldwell and Milton, 1988). Thus, it appears reasonable to speculate that aScTx-binding site and Na+ channel distributions are equivalent in muscle post-and perisynaptic membranes.…”

“…On the simple assumption that current density scales with channel density, Caldwell et al (1986) estimated the Na+ channel density on the NMJs to be up to x8000/ pm2. Nevertheless, Na+ current measurements on the end-plate are in agreement with an Na+ channel density higher than 2000/ pm* (Caldwell et al, 1986;Caldwell and Milton, 1988). If the ratio of Na+ channel density on extrasynaptic muscle surface to that in areas close to the NMJ is considered to be between 1:7 (Le.…”

“…Since TTX-resistant channels are undetectable in innervated adult muscle (Caldwell and Milton, 1988), they can be ruled out. Other muscle Na+ channel subtypes (Haimovich et al, 1984(Haimovich et al, , 1987 have been observed, and the possibility that one or several of these subtypes is not bound by otScTx cannot be excluded.…”

“…The density of AChRs in these crest areas is very high (about 1 0,000/~m2) (Heuser and Salpeter, 1979;Salpeter et al, 1984). Sodium channels are also distributed at higher densities in the synaptic and perisynaptic zones than on the muscle extrasynaptic surface, as shown by electrophysiological studies (Almers et al, 1983;Betz et al, 1984;Beam et al, 1985;Caldwell et al, 1986;Caldwell and Milton, 1988) and microscopic studies (Angelides, 1986;Dreyfus et al, 1986;Ariyasu et al, 1987;Haimovich et al, 1987;Boudier et al, 1988;Flucher and Daniels, 1989;Le Treut et al, 1990). Caldwell et al (1986) claimed that Na+ channel density was several thousand per square micrometer at the end-plate.…”

Key Role of Mucosal Primary Afferents in Mediating the Inhibitory Influence of Capsaicin on Vagally Mediated Contractions in the Mouse Esophagus

“…These electrical field stimulation-induced twitches could not be inhibited by d-tubocurarine, indicating that tetrodotoxin at this concentration not only blocks neural transmission but also directly inhibits the striated muscle contraction. Voltage-dependent sodium channels are distributed with different densities over the entire muscle cell membrane at least in skeletal muscles [2,3] and might reflect the sensitivity of esophageal striated muscle fibers to tetrodotoxin.…”