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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 272 |
| Issue number | 2 41-2 |
| State | Published - Feb 1997 |
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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 journal › Article
}
TY - JOUR
T1 - Mechanism of modulation of the voltage-gated skeletal and cardiac muscle sodium channels by fatty acids
AU - Bendahhou, Saïd
AU - Cummins, Theodore R.
AU - Agnew, William
PY - 1997/2
Y1 - 1997/2
N2 - 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.
AB - 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.
KW - arachidonic acid
KW - gating current
KW - inactivation
KW - ion channels
KW - ischemia
KW - potassium channels
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UR - http://www.scopus.com/inward/citedby.url?scp=0030934383&partnerID=8YFLogxK
M3 - Article
C2 - 9124303
AN - SCOPUS:0030934383
VL - 272
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 2 41-2
ER -