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

Abstract

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.

Tetrodotoxin suppresses morphological enhancement of the metastatic MAT-LyLu rat prostate cancer cell line

“…Gene products likely to influence morphological changes could include signalling molecules such as cell adhesion molecules (Hahn and Covault 1992;Itoh et al 1995) or receptors (Heathcote 1989). It is also possible that Na + channel activity may downregulate its own expression (Sherman and Catterall 1984) or alter the expression of other ion channels (FreudSilverberg and Shainberg 1993;Linsdell and Moody 1995).…”

Contribution of functional voltage‐gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. lateral motility

“…VGSC activity may regulate the expression of genes involved in motility e.g., cell adhesion molecules (Hahn and Covault, 1992;Itoh et al, 1995), receptors (Heathcote, 1989) and/or alter the expression of other ion channels (Freud-Silverberg and Shainberg, 1993;Linsdell and Moody, 1995).…”

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

“…There is a strong tendency toward high input resistance in immature neurons and muscle cells. This is seen in the development of mammalian central neurons (33,379,481,589,638), insect neuronal somata (155), and vertebrate skeletal muscle (236). Developmental decreases in resting resistance can be quite large, fivefold or more in some cases.…”

“…In mammalian skeletal muscle, innervation upregulates and denervation downregulates I IR expression (205), effects that appear to be secondary to activity-induced increases in [Ca 2ϩ ] i that stabilize IRK1 mRNA (540). Chloride channels also contribute to resting conductance, particularly in skeletal muscle, and their development appears to be dependent on innervation-induced electrical activity (236,293,482).…”

“…It also may have a functional role in matching ACh currents to the higher resting resistance of the slow muscle membrane. In fast-twitch muscle, nerve-induced activity suppresses the ␥-subunit synthesis and increases resting Cl conductance (236,581). This coordinates the development of the high mature resting conductance (see sect.…”