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

Saïd Bendahhou, Theodore R. Cummins, William S. Agnew

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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)
Pages (from-to)C592-C600
JournalAmerican Journal of Physiology - Cell Physiology
Issue number2 41-2
StatePublished - Feb 1997
Externally publishedYes


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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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