Potassium and chloride conductances in normal and denervated rat muscles

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.

Section: Introductionmentioning

confidence: 99%

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

Caldwell

Milton

1988

“…Muscle membrane becomes sensitive to ACh along its entire length (Axelsson & Thesleff, 1959;Miledi, 1960) due to an increase in the rate of AChR synthesis and its incorporation into the extrajunctional membrane (see Fambrough, 1979). In addition, the chloride conductance of denervated muscle is decreased from that of innervated muscle (Westgaard, 1975;Camerino & Bryant, 1976;Lorkovic & Tomanek, 1977;Harris & Betz, 1987). The experiments described in this paper showed that AChR and the chloride channel responsible for resting membrane conductance were regulated anticoordinate to one another.…”

Section: Introductionmentioning

confidence: 85%

Acetylcholine‐gated and chloride conductance channel expression in rat muscle membrane.

Heathcote

1989

SUMMARY1. During the differentiation of skeletal muscle, there is a synchronized expression of a number of muscle-specific proteins including the acetylcholine-gated ion channel (AChR). Another muscle-specific ion channel, responsible for chloride conductance, was shown to be expressed in an anticoordinate fashion to AChR. An organ culture system for rat lumbrical muscles was developed to manipulate the expression of these two ion channels.2. Denervation induced a change in expression of both channels that was mimicked in culture and reversed by direct electrical stimulation.3. The time course of the disappearance of both channels was similar and started immediately after denervation (chloride conductance) or stimulation (AChR). The time course of the appearance of AChR was delayed several days after denervation and culture but chloride conductance increased immediately upon stimulation.4. The loss of chloride conductance in muscle cultured in cycloheximide exhibited first-order kinetics, providing an estimate of the half-life (2-3 days) for the chloride conductance channel. This resembled the disappearance of chloride conductance in normal medium, suggesting that synthesis of this channel ceases following denervation. The decrease in chloride conductance characteristic of denervated muscle was not halted by cycloheximide.5. Changes in chloride conductance presumably alter the intracellular concentration of chloride. The possibility that chloride might regulate the expression of AChRs in skeletal muscle was tested by altering the intracellular concentration of chloride in muscles maintained in organ culture.6. Denervated muscles, whose intracellular concentration of chloride is elevated, were cultured in medium containing 9 mM-chloride (low-Cl-medium). AChR expression was reduced by either low-Cl-medium or electrical stimulation. Together, low-Cl-medium and electrical stimulation reduced expression more than either treatment alone.7. The loss of AChRs in low-Cl-medium was blocked when muscle fibrillation was halted by TTX.

“…Since blocking Gci in normal muscle with 9-AC greatly reduces the steady current (Betz et al 1984b), and since Gci falls 2-5-fold after denervation (Camerino & Bryant, 1976;Lorkovic & Tomanek, 1977), one might have predicted that the current would be reduced or abolished by denervation. All of the results suggested that the mechanism is essentially unchanged after denervation.…”

Section: Discussionmentioning

confidence: 99%

“…The reason for this difference is unknown; perhaps K+ conductance becomes insensitive to removal of external K+ after denervation, so that Vm follows changes in EK more closely (cf. Lorkovic & Tomanek, 1977).…”

Section: Discussionmentioning

confidence: 99%

“…In order to learn more about the characteristics of the endogenous steady current in muscle, we have studied the effects of denervation. Since GC1 falls dramatically after denervation (Camerino & Bryant, 1976;Lorkovic & Tomanek, 1977), and since blocking GC1 in normal muscle with drugs abolishes the steady current b), one might predict that the current would be reduced or absent after denervation. We found that the current persisted undiminished for at least 6 weeks after denervation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of denervation on a steady electric current generated at the end‐plate region of rat skeletal muscle.

Betz¹,

Caldwell²,

Harris³

1986

SUMMARY1. An electric current flows continuously out of the synaptic region of rat lumbrical muscle fibres. It is generated apparently as a result of a non-uniform Cl-conductance (GC1), with GC, being lowest at the end-plate.2. We investigated the effects of denervation on this current. The current persisted with little change after denervation. This was somewhat unexpected, since GC, falls dramatically after denervation, and in acute experiments on normal muscles, the steady current is greatly reduced by agents which block GC1.3. The steady current was blocked in denervated muscle, as in normal muscle, by low-Cl-solutions, Na+-free and K+-free solutions, and treatment with furosemide and 9-anthracene-carboxylic acid. The current in denervated muscle appears to be generated by the same general mechanism as in normal muscle. This has the effect of moving the Cl-equilibrium potential (EC,) in a positive direction, so that the driving force for passive Cl-efflux is increased. The increased driving force compensates for the reduced GC1, allowing the steady current to persist in denervated fibres.