Polyunsaturated fatty acids as anti-arrhythmic agents.

多不饱和脂肪酸作为抗心律失常剂。

基本信息

项目摘要

Project Summary The cardiac action potential is primarily generated by sodium and calcium channels, which depolarize the membrane potential, and by potassium channels that repolarize the membrane potential and terminate the action potential. One of the major cardiac potassium currents is the slowly activating potassium current IKs that contribute to the action potential termination. Over 300 different inherited mutations have been found in IKs channels that cause cardiac arrhythmias in patients. IKs channels regulate the length of the cardiac contraction and mutations that decreases the activity of IKs channels result in a prolongation of the cardiac contraction, leading to Long QT Syndrome. In turn, Long QT syndrome is a risk factor for ventricular fibrillation and sudden cardiac death. We have identified a family of compounds that activate IKs channels and are antiarrhythmic when applied to cardiomyocytes. We will here test whether these compounds restores the length of the action potential in human cardiomyocytes from Long QT Syndrome patients. We will also test the effect of these compounds on in ex vivo animal hearts and in vivo in transgenic animals with Long QT Syndrome mutations, in order to develop drug that restores the QT interval and that can be tested in future clinical trial. We will also test variants of these compounds on heterologously expressed IKs channels using two-electrode voltage clamp, to determine the important structure of these compounds for their effects on IKs channels. We will also make mutations of IKs channels to determine the binding site of these compounds. Finally, we will test the efficacy of these compounds to reverse different defects in IKs channels caused by different types of Long QT syndrome mutations. This will be tested both in heterologous systems and in human cardiomyocytes. The anticipated results of these experiments will provide proof-of-concept that this family of compounds can shorten the cardiac action potential and prevent cardiac arrhythmia, and will provide preliminary animal model data to start clinical trials of these compounds. We anticipate that this development of new anti-arrhythmic drugs will lead to better treatments of cardiac arrhythmias and the prevention of sudden cardiac deaths in LQTS patients.
项目总结

项目成果

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Derek Michael Dykxhoorn其他文献

Derek Michael Dykxhoorn的其他文献

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{{ truncateString('Derek Michael Dykxhoorn', 18)}}的其他基金

Polyunsaturated fatty acids as anti-arrhythmic agents.
多不饱和脂肪酸作为抗心律失常剂。
  • 批准号:
    10874097
  • 财政年份:
    2022
  • 资助金额:
    $ 11.29万
  • 项目类别:
Functional genomic studies in diverse populations to characterize risk loci for Alzheimer Disease
在不同人群中进行功能基因组研究,以确定阿尔茨海默病的风险位点
  • 批准号:
    10442439
  • 财政年份:
    2021
  • 资助金额:
    $ 11.29万
  • 项目类别:
Functional genomic studies in diverse populations to characterize risk loci for Alzheimer Disease
在不同人群中进行功能基因组研究,以确定阿尔茨海默病的风险位点
  • 批准号:
    10217547
  • 财政年份:
    2021
  • 资助金额:
    $ 11.29万
  • 项目类别:
Functional genomic studies in diverse populations to characterize risk loci for Alzheimer Disease
在不同人群中进行功能基因组研究,以确定阿尔茨海默病的风险位点
  • 批准号:
    10681312
  • 财政年份:
    2021
  • 资助金额:
    $ 11.29万
  • 项目类别:
Polyunsaturated fatty acids as anti-arrhythmic agents.
多不饱和脂肪酸作为抗心律失常剂。
  • 批准号:
    10369727
  • 财政年份:
    2016
  • 资助金额:
    $ 11.29万
  • 项目类别:
Polyunsaturated fatty acids as anti-arrhythmic agents.
多不饱和脂肪酸作为抗心律失常剂。
  • 批准号:
    10755511
  • 财政年份:
    2016
  • 资助金额:
    $ 11.29万
  • 项目类别:
Polyunsaturated fatty acids as anti-arrhythmic agents.
多不饱和脂肪酸作为抗心律失常剂。
  • 批准号:
    10210907
  • 财政年份:
    2016
  • 资助金额:
    $ 11.29万
  • 项目类别:
Polyunsaturated fatty acids as anti-arrhythmic agents.
多不饱和脂肪酸作为抗心律失常剂。
  • 批准号:
    10836101
  • 财政年份:
    2016
  • 资助金额:
    $ 11.29万
  • 项目类别:
TARGETED siRNA DELIVERY AS AN ANTI-HIV MICROBICIDE
靶向 siRNA 递送作为抗 HIV 杀菌剂
  • 批准号:
    8071962
  • 财政年份:
    2010
  • 资助金额:
    $ 11.29万
  • 项目类别:
TARGETED siRNA DELIVERY AS AN ANTI-HIV MICROBICIDE
靶向 siRNA 递送作为抗 HIV 杀菌剂
  • 批准号:
    8880097
  • 财政年份:
    2010
  • 资助金额:
    $ 11.29万
  • 项目类别:

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