Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.

Pepe, Salvatore; Bogdanov, K. Yu.; Hallaq, Haifa; Spurgeon, Harold A.; Leaf, Alexander; Lakatta, Edward G.

doi:10.1073/pnas.91.19.8832

Cited by 107 publications

(57 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pepe et al (32) confirmed that in adult rat cardiomyocytes an earlier finding that n Ϫ 3 PUFAs inhibited the action of dihydropyridine agonists and antagonists on the L-type Ca 2ϩ channels of neonatal rat ventricular myocytes (33). But using their whole cell patch clamp recordings, reported no inhibitory effect of the n Ϫ 3 PUFAs on the L-type Ca 2ϩ currents per se.…”

Section: Discussionsupporting

confidence: 75%

Suppression of voltage-gated L-type Ca ²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

Xiao

Gómez²,

Lederer³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

357

234

View full text Add to dashboard Cite

Our recent data show that in cardiac myocytes polyunsaturated fatty acids (PUFAs) are antiarrhythmic. They reduce I Na , shorten the action potential, shift the threshold for excitation to more positive potentials, and prolong the relative refractory period. In this study we use patch-clamp techniques in whole-cell mode and confocal Ca 2؉ imaging to examine the effects of PUFAs on the voltage-gated L-type Ca 2؉ current (I Ca,L ), elementary sarcoplasmic reticulum Ca 2؉ -release events (Ca 2؉ -sparks), and [Ca 2؉ ] i transients in isolated rat ventricular myocytes. Extracellular application of eicosapentaenoic acid (EPA; C20:5 n ؊ 3) produced a prompt and reversible concentration-dependent suppression of I Ca,L . The concentration of EPA to produce 50% inhibition of I Ca was 0.8 M in neonatal rat heart cells and 2.1 M in adult ventricular myocytes. While the EPA induced suppression of I Ca,L , it did not significantly alter the shape of the current-voltage relation but did produce a small, but significant, negative shift of the steady-state inactivation curve. The inhibition of I Ca,L was voltage-and time-dependent, but not use-or frequency-dependent. Other PUFAs, such as docosahexaenoic acid, arachidonic acid, linolenic acid, linoleic acid, conjugated linoleic acid, and eicosatetraynoic acid had similar effects on I Ca,L as EPA. All-trans-retinoic acid, which had been shown to suppress induced arrhythmogenic activity in rat heart cells, also produced a significant inhibition of I Ca,L . The saturated stearic acid and the monounsaturated oleic acid had no effect on I Ca,L . Because both I Ca,L and sarcoplasmic reticulum Ca 2؉ -release underlie many cardiac arrhythmias, we examined the effects of EPA on I Ca,L and Ca 2؉ -sparks. While EPA suppressed both, it did not change the temporal or spatial character of the Ca 2؉ -sparks, nor did it alter the ability of I Ca,L to trigger Ca 2؉ -sparks. We conclude that PUFAs may act as antiarrhythmic agents in vivo in normal and Ca 2؉ -overloaded cells principally because they reduce Ca 2؉ entry by blocking I Ca,L . Furthermore, PUFAs act directly to decrease I Na and I Ca,L , but indirectly to reduce the [Ca 2؉ ] i transients and [Ca 2؉ ] i -activated membrane current. Although a negative inotropic action is associated with application of PUFAs, it is clear that by reducing I Ca,L , I Na and Ca 2؉ -sparks, PUFAs can reduce spontaneous extrasystoles in the heart. The mechanisms by which PUFAs act are discussed.

show abstract

Section: Discussionsupporting

confidence: 75%

Suppression of voltage-gated L-type Ca ²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

Xiao

Gómez²,

Lederer³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

357

234

View full text Add to dashboard Cite

show abstract

“…The data, therefore, were fit up to 40 ,uM with the Hill coefficient set at 2 and a maximal effect of -8.3 + 0.1 mV and an EC50 of 17.8 0.2 ,uM were found, the latter of which is probably better stated as simply >15 AM. It was reported that, in neonatal rat cardiomyocytes, DHA had no direct effect on the L-type calcium channels (22).…”

Section: Resultsmentioning

confidence: 99%

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

Vreugdenhil

Bruehl²,

Voskuyl³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

274

175

View full text Add to dashboard Cite

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 CAl neurons freshly isolated from the rat hippocampus. Extracellular application of PUFAs produced a concentrationdependent 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 ,uM for docosahexaenoic acid (DHA) and 4 + 0.4 ,uM for eicosapentaenoic acid (EPA). The EC50 for the shift on the ICa inactivation curve was 2.1 + 0.4 for DHA and >15 ,uM for EPA. Additionally, DHA

show abstract

“…Using patch clamp techniques, Poling et al [145,146] reported that non-esterified DHA interacts with an external channel domain and regulates the activity of certain voltage-gated K + channels in a Zn 2+ -dependent fashion. PUFA have additionally been shown to modulate L-type Ca 2+ channels [147,148], suggesting a role in cell signaling. Hasler et al [149] reported that 50 µM DHA inhibited gap junction intercellular communication by 18% while several other fatty acids had no measurable effect.…”

Section: Dha: Affect On Cell Signaling and Apoptosismentioning

confidence: 99%

Docosahexaenoic acid affects cell signaling by altering lipid rafts

et al. 2005

View full text Add to dashboard Cite

-With 22 carbons and 6 double bonds docosahexaenoic acid (DHA) is the longest and most unsaturated fatty acid commonly found in membranes. It represents the extreme example of a class of important human health promoting agents known as omega-3 fatty acids. DHA is particularly abundant in retinal and brain tissue, often comprising about 50% of the membrane's total acyl chains. Inadequate amounts of DHA have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities to depression and suicide. The molecular mode of action of DHA, while not yet understood, has been the focus of our research. Here we briefly summarize how DHA affects membrane physical properties with an emphasis on membrane signaling domains known as rafts. We report the uptake of DHA into brain phosphatidylethanolamines and the subsequent exclusion of cholesterol from the DHA-rich membranes. We also demonstrate that DHA-induced apoptosis in MDA-MB-231 breast cancer cells is associated with externalization of phosphatidylserine and membrane disruption ("blebbing"). We conclude with a proposal of how DHA incorporation into membranes may control cell biochemistry and physiology. apoptosis / docosahexaenoic acid / lipid rafts / membranes / phospholipids

show abstract

Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.

Abstract: The effect of docosahexaenoic acid (DHA; C22

Cited by 107 publications

References 14 publications

Suppression of voltage-gated L-type Ca ²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

Suppression of voltage-gated L-type Ca ²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

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

Docosahexaenoic acid affects cell signaling by altering lipid rafts

Contact Info

Product

Resources

About

Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.

Abstract: The effect of docosahexaenoic acid (DHA; C22

Cited by 107 publications

References 14 publications

Suppression of voltage-gated L-type Ca 2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

Suppression of voltage-gated L-type Ca 2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

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

Docosahexaenoic acid affects cell signaling by altering lipid rafts

Contact Info

Product

Resources

About

Suppression of voltage-gated L-type Ca ²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

Suppression of voltage-gated L-type Ca ²⁺ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes