Modulation of native T-type calcium channels by ω-3 fatty acids

Danthi, Sanjay; Enyeart, Judith A.; Enyeart, John J.

doi:10.1016/j.bbrc.2004.12.033

Cited by 51 publications

(42 citation statements)

References 36 publications

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“…Membranes enriched in C:22 -3 PUFAs demonstrate significant increases in membrane fluidity and lipid raft formation (for review, see Stillwell and Wassall, 2003) and can directly or indirectly affect the function of a number of membrane proteins, such as receptors (Yamashima, 2008;Lafourcade et al, 2011) and ion channels (Lauritzen et al, 2000;Danthi et al, 2005;Ye et al, 2010). -3 PUFAs are also known to act as a ligand for the retinoid X receptor (RXR) and activate peroxisome proliferatoractivated receptors.…”

Section: Discussionmentioning

confidence: 99%

Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids

Gladman¹,

Huang²,

Lim³

et al. 2012

J. Neurosci.

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Functional recovery after a peripheral nerve injury (PNI) is often poor. There is a need for therapies that protect neurons against injury and enhance regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury. The objective of this study was to assess the neuroprotective and proregenerative potential of -3 PUFAs in PNI. We investigated this in mice that express the fat-1 gene encoding for -3 fatty acid desaturase, which leads to an increase in endogenous -3 PUFAs and a concomitant decrease in -6 PUFAs. Dorsal root ganglion (DRG) neurons from wild-type or fat-1 mice were subjected to a mechanical strain or hypoxic injury, and cell death was assessed using ethidium homodimer-1 labeling. The fat-1 background appears to confer robust neuroprotection against both injuries. We then examined the early functional and morphological changes in wild-type and fat-1 mice after a sciatic nerve crush. An accelerated functional recovery 7 d after injury was seen in fat-1 mice when assessed using von Frey filaments and the sciatic nerve functional index. These observations were also mapped to changes in injury-related markers. The injury-induced expression of ATF-3 was decreased in the DRG of fat-1 mice, whereas the axons detected 6 mm distal to the crush were increased. Fat-1 animals also had some protection against muscle atrophy after injury. In conclusion, both in vitro and in vivo experiments support the idea that a higher endogenous -3 PUFA could lead to beneficial effects after a PNI.

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Section: Discussionmentioning

confidence: 99%

Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids

Gladman¹,

Huang²,

Lim³

et al. 2012

J. Neurosci.

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“…9,[33][34][35] In humans, n-3 PUFA supplementation reduced the QT interval. 36 A similar amelioration of repolarization parameters was demonstrated in our study.…”

Section: Discussionmentioning

confidence: 99%

“…n-3 PUFAs putatively affect membrane ion channels. 9,10 They exert antihypertensive, antiproliferative, anti-inflammatory, and anticoagulative properties. 11 In spontaneously hypertensive rats, n-3 PUFA treatment lowered blood pressure.…”

mentioning

confidence: 99%

Dietary n-3 Polyunsaturated Fatty Acids and Direct Renin Inhibition Improve Electrical Remodeling in a Model of High Human Renin Hypertension

et al. 2008

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Abstract-We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA-or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180Ϯ3 mm Hg) compared with dTGRs (208Ϯ5 mm Hg). Aliskiren-treated dTGRs and SpragueDawley rats were normotensive (110Ϯ3 and 119Ϯ6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT c intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy. Key Words: angiotensin II Ⅲ renin inhibition Ⅲ n-3 PUFA Ⅲ arrhythmias Ⅲ magnetocardiography H ypertensive heart disease causes heart failure and arrhythmia propensity. Ischemia, cardiac hypertrophy, fibrosis, inflammation, and electrical remodeling all contribute to the pathogenesis. 1,2 The renin-angiotensin-aldosterone system is a primary driver, and its blockade is state-of-the-art therapy. We provided initial evidence that direct renin inhibition (DRI) in transgenic rats harboring the human renin and angiotensinogen genes (dTGRs) improves target organ damage. 3-5 Untreated dTGRs developed severe hypertension, hypertrophy, inflammation, fibrosis, and small myocardial infarctions. Ventricular arrhythmias and, consequently, sudden cardiac death contributed to the high mortality rate at the early age of 7 weeks. 6 Electrical remodeling in dTGRs included dysregulation of the I to potassium channel, Ca 2ϩ -cycling proteins, and connexin (Cx) 43 gap junctions. 6,7 n-3 polyunsaturated fatty acids (PUFAs), contained in marine fish oil, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lead to cardioprotection and reduce sudden cardiac death. 8 The molecular mechanisms by which n-3 PUFAs exert their cardioprotective effects are not fully understood. n-3 PUFAs putatively affect membran...

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“…124 -129 T-type Ca 2ϩ channels also serve as a point of Ca 2ϩ entry for atrial cardiomyocytes and for specialized conduction cells, and short-term application of DHA, EPA, or ALA can reduce T-type Ca 2ϩ entry in adrenal glomerulosa cells. 130 We are aware of no studies to test the effects of dietary n-3 fatty acid supplementation on L-or T-type Ca 2ϩ channel function or expression. Lack of data on Ca 2ϩ entry in dietary models is a e328 Circulation September 4, 2007 significant knowledge gap.…”

Section: Potassium Channelsmentioning

confidence: 99%

Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research

et al. 2007

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Modulation of native T-type calcium channels by ω-3 fatty acids

Cited by 51 publications

References 36 publications

Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids

Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids

Dietary n-3 Polyunsaturated Fatty Acids and Direct Renin Inhibition Improve Electrical Remodeling in a Model of High Human Renin Hypertension

Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research

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