Transient outward potassium channel regulation in healthy and diabetic heartsThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).

Gallego, Mónica; Alday, Aintzane; Urrutia, Janire; Casis, Óscar

doi:10.1139/y08-106

Cited by 21 publications

(10 citation statements)

References 43 publications

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“…The findings in failing hearts suggest that reduced repolarizing currents including I to are implicated in the pathogenesis of acquired QT prolongation (30). Indeed, previous studies (16-18) and our present results indicate that myocytes isolated from diabetic hearts show a reduction in I to currents. Changes in the expression of Kv channel genes have been suggested to underlie the I to remodeling.…”

Section: Discussionsupporting

confidence: 80%

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Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

Xiang

Xiao

et al. 2012

Braz J Med Biol Res

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Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (Ito) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg−1·day−1). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of Ito was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated Ito reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced Ito of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.

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Section: Discussionsupporting

confidence: 80%

“…While Kv1.4 is responsible for I to,s channels, both Kv4.2 and Kv4.3 contribute to I to,f channels (15). Down-regulation of I to is a consistent finding in diabetic hearts (16-18). However, at present, the mechanism(s) by which DM influences the density of cardiac I to is not completely understood.…”

Section: Introductionsupporting

confidence: 56%

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

Xiang

Xiao

et al. 2012

Braz J Med Biol Res

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“…Therefore, Kv channels toxins constitute potential drugs for the treatment of a variety of diseases like cancer, immunological, metabolic, neurological and cardiovascular disorders [28,29,30,31,32,33,34]. Additionally, studying isolated scorpion toxins can contribute to a better understanding of the scorpion envenoming syndrome and to the development of more effective antivenoms.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological Characterization of Ts6 and Ts7, K+ Channel Toxins Isolated through an Improved Tityus serrulatus Venom Purification Procedure

Cerni

Pucca

Peigneur

et al. 2014

Toxins

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In Brazil, Tityus serrulatus (Ts) is the species responsible for most of the scorpion related accidents. Among the Ts toxins, the neurotoxins with action on potassium channels (α-KTx) present high interest, due to their effect in the envenoming process and the ion channel specificity they display. The α-KTx toxins family is the most relevant because its toxins can be used as therapeutic tools for specific target cells. The improved isolation method provided toxins with high resolution, obtaining pure Ts6 and Ts7 in two chromatographic steps. The effects of Ts6 and Ts7 toxins were evaluated in 14 different types of potassium channels using the voltage-clamp technique with two-microelectrodes. Ts6 toxin shows high affinity for Kv1.2, Kv1.3 and Shaker IR, blocking these channels in low concentrations. Moreover, Ts6 blocks the Kv1.3 channel in picomolar concentrations with an IC50 of 0.55 nM and therefore could be of valuable assistance to further designing immunosuppressive therapeutics. Ts7 toxin blocks multiple subtypes channels, showing low selectivity among the channels analyzed. This work also stands out in its attempt to elucidate the residues important for interacting with each channel and, in the near future, to model a desired drug.

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“…Diabetes significantly modifies action potential, Ca 2+ transient and Ca 2+ sensitivity of contractile elements in cardiomyocytes [62–66]. Prolongation of action potential duration (APD) and slower decay of Ca 2+ transient are consistently observed in diabetic cardiomyocytes.…”

Section: Mechanism Of Contractile Dysfunction Of Diabetic Myocardiummentioning

confidence: 99%

Diabetic cardiomyopathy: pathophysiology and clinical features

et al. 2012

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Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and modifies intracellular signaling, leading to impairments in multiple steps of excitation–contraction coupling, inefficient energy production, and increased susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and remodeling of the extracellular matrix are also involved in contractile dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques (tissue Doppler imaging and strain rate imaging) and magnetic resonance spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and a combination of the modalities allows differentiation of this type of cardiomyopathy from other organic heart diseases. Circumstantial evidence to date indicates that diabetic cardiomyopathy is a common but frequently unrecognized pathological process in asymptomatic diabetic patients. However, a strategy for prevention or treatment of diabetic cardiomyopathy to improve its prognosis has not yet been established. Here, we review both basic and clinical studies on diabetic cardiomyopathy and summarize problems remaining to be solved for improving management of this type of cardiomyopathy.

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Transient outward potassium channel regulation in healthy and diabetic heartsThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue).

Cited by 21 publications

References 43 publications

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

Electrophysiological Characterization of Ts6 and Ts7, K+ Channel Toxins Isolated through an Improved Tityus serrulatus Venom Purification Procedure

Diabetic cardiomyopathy: pathophysiology and clinical features

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