The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte

Wu, Chau‐Chung; Su, Ming‐Jai; Chi, Jo-Feng; Chen, Wen‐Jone; Hsu, Hsiu-Ching; Lee, Yuan‐Teh

doi:10.1016/s0022-2828(05)82388-0

Cited by 39 publications

(29 citation statements)

References 31 publications

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“…Control rabbits were maintained on standard calibrated chow (Purina 5321), and the CF rabbits were fed batch-matched standard chow supplemented with 0.5% cholesterol (Wako Co) and coconut oil (Yeali Co) for up to 12 weeks. 20 Every 3 weeks after initiation of the cholesterol-enriched diet, we executed echocardiography, examined the serum levels of total cholesterol and triglyceride, and killed five animals to harvest the hearts. After completing the 12-week feeding protocol, the residual five hypercholesterolemic rabbits continued feeding on standard chow for 18 weeks to study the effects of dietary cholesterol withdrawal (cholesterol-withdrawn, CW).…”

Section: Animalsmentioning

confidence: 99%

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Lin

Yeh

et al. 2005

Laboratory Investigation

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The effects of hypercholesterolemia on the myocardium per se include electrophysiological and mechanical alterations. Since gap junctions are essential in electromechanical coupling throughout the heart, we examined the correlation between the temporal expression of cardiac connexin 43 (Cx43), contractile function, and conduction velocity in cholesterol-fed rabbits. After a 12-week feeding period, serum cholesterol levels gradually increased (Po0.001). In contrast, expression of cardiomyocyte Cx43 protein progressively decreased (60% reduction at 12 weeks, Po0.001). Such a reduction was also demonstrated by immunoconfocal microscopy, which further showed redistribution of Cx43 gap junctions at the lateral cell membrane. The downregulation of Cx43 protein was associated with increased levels of Cx43 mRNA (3.5 -fold at 12 weeks, Po0.001) and phosphorylated c-Jun N-terminal kinase (three-fold at 12 weeks, P ¼ 0.001). Functionally, although fractional shortening of the left ventricle remained unchanged throughout the feeding protocol, the cholesterol-fed rabbits had a reduced cardiac cycle-dependent variation of integrated backscatters, a decreased mitral ring systolic velocity, and an increased modified Tei index (all Po0.001), all of which indicated impaired intrinsic myocardial contractility and attenuated ventricular systolic performance. In Langendorff-perfused hearts of cholesterol-fed rabbits, decreased conduction velocity was observed (Po0.005). Withdrawal of the cholesterol-enriched diet for 18 weeks restored the contractile parameters and Cx43 protein expression. These findings suggest that Cx43 is highly involved in the molecular mechanism of hypercholesterolemia-induced cardiac contractile dysfunction and dysrhythmias.

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Section: Animalsmentioning

confidence: 99%

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Lin

Yeh

et al. 2005

Laboratory Investigation

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“…Multiple studies have shown that an increase in membrane cholesterol regulates the function of a variety of ion channels (1,2), including different types of K ϩ channels (3)(4)(5)(6)(7)(8), Ca 2ϩ channels (9 -13), Na ϩ channels (14,15), and Cl Ϫ channels (16,17). The most common effect of cholesterol on ion channels is a decrease in channel activity that may include a decrease in the open probability, in the unitary conductance, and/or in the number of active channels in the membrane.…”

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confidence: 99%

Distant Cytosolic Residues Mediate a Two-way Molecular Switch That Controls the Modulation of Inwardly Rectifying Potassium (Kir) Channels by Cholesterol and Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)

Rosenhouse‐Dantsker

Noskov

Han

et al. 2012

Journal of Biological Chemistry

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Background: Cholesterol modulates inwardly rectifying potassium (Kir) channels. Results: A two-way molecular cytosolic switch controls channel modulation by cholesterol and PI(4,5)P 2 . Conclusion: Cholesterol and PI(4,5)P 2 induce a common gating pathway of Kir2.1 despite their opposite impact on channel function. Significance: These findings provide insights into structure-function relationship of ion channels and contribute to understanding of the mechanisms underlying their regulation by lipids.

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“…This is in agreement with previously published results in a rabbit model of hypercholesterolemia where a 40% increase of plasma membrane cholesterol content was associated with a 38% decrease in I Na in ventricular myocytes, without a change of inactivation of I Na . 33 Together, these data suggest that alterations of I Na are not the cause of the AP and QTc prolongation.…”

Section: Discussionmentioning

confidence: 83%

Dyscholesterolemia Protects Against Ischemia-Induced Ventricular Arrhythmias

Baartscheer

Schumacher

Wekker

et al. 2015

Circ: Arrhythmia and Electrophysiology

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The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte

Cited by 39 publications

References 31 publications

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Downregulated myocardial connexin 43 and suppressed contractility in rabbits subjected to a cholesterol-enriched diet

Distant Cytosolic Residues Mediate a Two-way Molecular Switch That Controls the Modulation of Inwardly Rectifying Potassium (Kir) Channels by Cholesterol and Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)

Dyscholesterolemia Protects Against Ischemia-Induced Ventricular Arrhythmias

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