کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5827414 1558927 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cardiovascular pharmacologyThe effects of A-803467 on cardiac Nav1.5 channels
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Cardiovascular pharmacologyThe effects of A-803467 on cardiac Nav1.5 channels
چکیده انگلیسی

A-803467 is a selective Nav1.8 blocker, but its mechanism of action at cardiac sodium channels is uncertain. Thus, we investigated the mechanistic effects of A-803467 on cardiac sodium channels in isolated mouse ventricular myocytes and in human embryonic kidney 293 (HEK293) cell lines that transiently expressed Nav1.5/SCN5A, the predominant cardiac sodium channel. At 0.3 μM and greater, A-803467 blocked cardiac sodium currents in a dose-dependent manner in both ventricular myocytes and in SCN5A-expressing HEK293 cell lines. In both models, the drug caused significant depolarizing shifts at the conductance voltage relationship midpoint, hyperpolarizing shifts in voltage-dependent channel inactivation, and slower recovery from inactivation. Also, the drug reduced sodium current amplitude in a frequency-dependent manner, and blocked late sodium currents, accelerated inactivation, and enhanced the intermediate inactivation state. Our results provide strong evidence that A-803467 affects multiple biophysical characteristics of the canonical cardiac Nav1.5 channel and our data can be used to study potential applications of A-803467 as an antiarrhythmic drug.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 754, 5 May 2015, Pages 52-60
نویسندگان
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