Mechanism of modulation of the voltage-gated skeletal and cardiac muscle sodium channels by fatty acids

Saïd Bendahhou, Theodore R. Cummins, William Agnew

Research output: Contribution to journalArticle

Abstract

Voltage-gated rat skeletal muscle and cardiac Na+ channels are modulated by exogenous unsaturated fatty acids. Application of 1-10 μM arachidonic or oleic acids reversibly depressed Na+ channel conductance and shifted the inactivation curve to hyperpolarizing potentials. These effects were not prevented by inhibitors of lipoxygenase, cyclooxygenase, cytochrome P-450 epoxygenase, or protein kinase C. Neither palmitic acid nor methyl ester oleate had an effect on the inward Na+ current, suggesting that trivial variations in membrane fluidity are not responsible for the Na+ current depression or kinetic changes. Arachidonic acid altered fast Na+ inactivation without changing the slow inactivation kinetics. Moreover, skeletal muscle Na+ channel gating currents were markedly decreased by 2 μM arachidonic acid. Finally, nonstationary noise analysis indicated that both the number of channels and the open probability were slightly decreased without change in the single-channel conductance. These data suggest that unsaturated fatty acids such as arachidonic and oleic acids 1) specifically regulate voltage-gated Na+ channels and 21 interact directly with Na+ channels, perhaps at a fatty acid binding domain, by decreasing the total gating charge and altering fast-inactivation kinetics.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume272
Issue number2 41-2
StatePublished - Feb 1997

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Sodium Channels
Oleic Acids
Arachidonic Acids
Muscle
Myocardium
Skeletal Muscle
Fatty Acids
Modulation
Unsaturated Fatty Acids
Arachidonic Acid
Kinetics
Electric potential
Lipoxygenase Inhibitors
Membrane Fluidity
Cyclooxygenase Inhibitors
Palmitic Acid
Fluidity
Oleic Acid
Prostaglandin-Endoperoxide Synthases
Cytochrome P-450 Enzyme System

Keywords

  • arachidonic acid
  • gating current
  • inactivation
  • ion channels
  • ischemia
  • potassium channels

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Mechanism of modulation of the voltage-gated skeletal and cardiac muscle sodium channels by fatty acids. / Bendahhou, Saïd; Cummins, Theodore R.; Agnew, William.

In: American Journal of Physiology - Cell Physiology, Vol. 272, No. 2 41-2, 02.1997.

Research output: Contribution to journalArticle

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