Effects of ethanol on voltage-sensitive Na-channels in cultured skeletal muscle: Up-regulation as a result of chronic treatment

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6207451

Brodie, C; Sampson, S R ^[1]

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1. Bar-Ilan Univ., Ramat-Gan (Israel)

The effects of acute and chronic treatment with ethanol were studied on the number and activity of tetrodotoxin-sensitive Na-channels in cultured rat skeletal muscle. The number of channels was determined by measurements of specific binding of (3H) saxitoxin (STX) in whole cell preparations. Measurements were also made of the frequency and rate of rise of spontaneously occurring action potentials, which are the physiologic expression of Na-channel density. Acute ethanol (37.5-150 mM), while causing depolarization of membrane potential and blockade of electrical activity, was without effect on specific STX binding. Neither methanol, acetaldehyde nor ethylene glycol had significant effects on these properties when given acutely in the same concentrations as ethanol. Chronic ethanol caused dose-related increases in STX binding and action potential properties with maximal levels being attained after 3 days of treatment at a concentration of 150 mM. On removal of ethanol from the culture medium all properties returned to control levels after 48 hr. Both increased external K+ and tetrodotoxin, which up-regulate Na-channels by reducing cytosolic Ca++, potentiated the ethanol-induced increase in Na-channel density. The increase in STX binding was not associated with changes in affinity of the binding sites for the ligand but was completely prevented by treatment with cycloheximide and actinomycin D. The results demonstrate that ethanol interacts with the cell membrane to induce synthesis of STX-binding sites.

• OSTI ID: 6207451
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 255:3; ISSN 0022-3565; ISSN JPETA
• Country of Publication: United States
• Language: English

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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACUTE EXPOSURE
ALCOHOLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CELL MEMBRANES
CHRONIC EXPOSURE
DOSE-RESPONSE RELATIONSHIPS
ELECTROPHYSIOLOGY
ETHANOL
GLYCOPROTEINS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
METABOLISM
MUSCLES
ORGANIC COMPOUNDS
PHYSIOLOGY
PREGNANCY
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES