Home LiteratureArticle Details
PMID: 8901621 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 22 ·1996-10-29 ·Pages 12559-63

Vreugdenhil M, Bruehl C, Voskuyl RA, Kang JX, Leaf A, Wadman WJ

Abstract

Recent evidence indicates that long-chain polyunsaturated fatty acids (PUFAs) can prevent cardiac arrhythmias by a reduction of cardiomyocyte excitability. This was shown to be due to a modulation of the voltage-dependent inactivation of both sodium (INa) and calcium (ICa) currents. To establish whether PUFAs also regulate neuronal excitability, the effects of PUFAs on INa and ICa were assessed in CA1 neurons freshly isolated from the rat hippocampus. Extracellular application of PUFAs produced a concentration-dependent shift of the voltage dependence of inactivation of both INa and ICa to more hyperpolarized potentials. Consequently, they accelerated the inactivation and retarded the recovery from inactivation. The EC50 for the shift of the INa steady-state inactivation curve was 2.1 +/- 0.4 microM for docosahexaenoic acid (DHA) and 4 +/- 0.4 microM for eicosapentaenoic acid (EPA). The EC50 for the shift on the ICa inactivation curve was 2.1 +/- 0.4 for DHA and > 15 microM for EPA. Additionally, DHA and EPA suppressed both INa and ICa amplitude at concentrations > 10 microM. PUFAs did not affect the voltage dependence of activation. The monounsaturated oleic acid and the saturated palmitic acid were virtually ineffective. The combined effects of the PUFAs on INa and ICa may reduce neuronal excitability and may exert anticonvulsive effects in vivo.

MeSH Terms
Animals Calcium Channels/drug effects,metabolism Docosahexaenoic Acids/administration & dosage,pharmacology Dose-Response Relationship, Drug Eicosapentaenoic Acid/administration & dosage,pharmacology Fatty Acids, Unsaturated/administration & dosage,pharmacology Hippocampus/cytology,metabolism Male Neurons/drug effects,metabolism Oleic Acid/administration & dosage,pharmacology Pyramidal Cells/drug effects,metabolism Rats Rats, Wistar Sodium Channels/drug effects,metabolism
Chemicals
Calcium Channels Fatty Acids, Unsaturated Sodium Channels Docosahexaenoic Acids Oleic Acid Eicosapentaenoic Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Vreugdenhil M
Institute of Neurobiology, University of Amsterdam, The Netherlands.
Bruehl C
Voskuyl R A
Kang J X
Leaf A
Wadman W J
References (31)
31 references, click to expand
  1. Influence of dietary n-3 fatty acids on myocardial ischemia and reperfusion.
    Am J Physiol. 1990 Nov;259(5 Pt 2):H1518-26 PMID: 2240249
  2. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds.
    Pharmacol Rev. 1990 Sep;42(3):223-86 PMID: 2217531
  3. Essential fatty acids: the importance of n-3 fatty acids in the retina and brain.
    Nutr Rev. 1992 Apr;50(4 ( Pt 2)):21-9 PMID: 1608561
  4. Enhancement of calcium currents in rat hippocampal CA1 neurons induced by kindling epileptogenesis.
    Neuroscience. 1992 Jul;49(2):373-81 PMID: 1331856
  5. External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1937-41 PMID: 8127910
  6. Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.
    Proc Natl Acad Sci U S A. 1994 May 10;91(10):4427-30 PMID: 8183925
  7. Facilitatory effect of docosahexaenoic acid on N-methyl-D-aspartate response in pyramidal neurones of rat cerebral cortex.
    J Physiol. 1994 Feb 15;475(1):83-93 PMID: 7514666
  8. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.
    Lancet. 1994 Jun 11;343(8911):1454-9 PMID: 7911176
  9. Essential fatty acid preparation (SR-3) raises the seizure threshold in rats.
    Eur J Pharmacol. 1994 Mar 11;254(1-2):193-8 PMID: 7911428
  10. Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9886-90 PMID: 7937911
  11. Modulation of ion channels by arachidonic acid.
    Prog Neurobiol. 1994 Jun;43(2):175-86 PMID: 7526418
  12. Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation.
    Lancet. 1995 Jan 14;345(8942):91-5 PMID: 7815888
  13. Time- and voltage-dependent block of delayed rectifier potassium channels by docosahexaenoic acid.
    Mol Pharmacol. 1995 Feb;47(2):381-90 PMID: 7870048
  14. Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes.
    Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3997-4001 PMID: 7732020
  15. Arachidonic acid activation of a new family of K+ channels in cultured rat neuronal cells.
    J Physiol. 1995 May 1;484 ( Pt 3):643-60 PMID: 7623282
  16. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest.
    JAMA. 1995 Nov 1;274(17):1363-7 PMID: 7563561
  17. Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes.
    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11000-4 PMID: 7479925
  18. Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins.
    Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3542-6 PMID: 8622972
  19. Role of essential fatty acids in the function of the developing nervous system.
    Lipids. 1996 Mar;31 Suppl:S167-76 PMID: 8729114
  20. Effect of arachidonic acid on the L-type calcium current in frog cardiac myocytes.
    J Physiol. 1996 May 15;493 ( Pt 1):67-81 PMID: 8735695
  21. Protective effects of free polyunsaturated fatty acids on arrhythmias induced by lysophosphatidylcholine or palmitoylcarnitine in neonatal rat cardiac myocytes.
    Eur J Pharmacol. 1996 Feb 15;297(1-2):97-106 PMID: 8851173
  22. Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat.
    J Neurophysiol. 1996 Mar;75(3):1264-70 PMID: 8867135
  23. Lidocaine block of cardiac sodium channels.
    J Gen Physiol. 1983 May;81(5):613-42 PMID: 6306139
  24. Influence of dietary lipids on arrhythmias and infarction after coronary artery ligation in rats.
    Can J Physiol Pharmacol. 1985 Nov;63(11):1411-7 PMID: 4075259
  25. Kinetics of protein binding determine rates of uptake of drugs by brain.
    Am J Physiol. 1986 Dec;251(6 Pt 2):R1212-20 PMID: 3789202
  26. NMDA receptors activate the arachidonic acid cascade system in striatal neurons.
    Nature. 1988 Nov 3;336(6194):68-70 PMID: 2847054
  27. Determination of the threshold for convulsions by direct cortical stimulation.
    Epilepsy Res. 1989 Mar-Apr;3(2):120-9 PMID: 2707249
  28. Phenytoin and carbamazepine: potential- and frequency-dependent block of Na currents in mammalian myelinated nerve fibers.
    Epilepsia. 1989 May-Jun;30(3):286-94 PMID: 2542011
  29. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).
    Lancet. 1989 Sep 30;2(8666):757-61 PMID: 2571009
  30. Action of antiepileptic and anaesthetic drugs on Na- and Ca-spikes in mammalian non-myelinated axons.
    Eur J Pharmacol. 1990 Jan 10;175(2):155-63 PMID: 2311652
  31. Direct regulation of ion channels by fatty acids.
    Trends Neurosci. 1991 Mar;14(3):96-100 PMID: 1709540
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.22.12559
Published
1996-10-29
Pages
12559-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38031
Subset
IM
Grants
NIDDK NIH HHS · DK38165 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.22.12559 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2