کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10954245 | 1097869 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Post-transcriptional gene silencing of KChIP2 and Navβ1 in neonatal rat cardiac myocytes reveals a functional association between Na and Ito currents
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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![عکس صفحه اول مقاله: Post-transcriptional gene silencing of KChIP2 and Navβ1 in neonatal rat cardiac myocytes reveals a functional association between Na and Ito currents Post-transcriptional gene silencing of KChIP2 and Navβ1 in neonatal rat cardiac myocytes reveals a functional association between Na and Ito currents](/preview/png/10954245.png)
چکیده انگلیسی
The Ca2+-independent transient outward potassium current (Ito) encoded by the Kv4 family of potassium channels, is central to normal repolarization of cardiac myocytes. KChIPs are a group of Ca2+-binding accessory subunits that modulate Kv4-encoded currents. However, the biophysical effects of KChIP2 on Kv4 currents raise questions about the role that KChIP2 plays in forming the native Ito. Previous heterologous expression studies demonstrated that the Na channel β1 subunit modulates the gating properties of Kv4.3 to closely recapitulate native Ito suggesting that Navβ1 may modulate the function of Kv4-encoded channels in native cardiomyocytes. Therefore we hypothesized the existence of a structural or functional complex between subunits of Ito and INa. In co-immunoprecipitation of proteins from neonatal rat ventricular myocardium (NRVM), Navβ1 was pulled-down by Kv4.x antibodies suggesting a structural association between subunits that comprise Ito and INa. Remarkably, post-transcriptional gene silencing of KChIP2 in NRVM, using small interfering RNAs specific to KChIP2, suppressed both cardiac Ito and INa consistent with a functional coupling of these channels. KChIP2 silencing suppressed Na channel α and β1 subunit mRNA levels, leaving Kv4.x mRNAs unaltered, but reducing levels of immunoreactive proteins. Post-transcriptional gene silencing of Navβ1 reduced its protein expression. Silencing of Navβ1 also reduced mRNA and protein levels of its α-subunit, Nav1.5. Surprisingly, silencing of Navβ1 also produced a reduction in KChIP2 mRNA and protein as well as Kv4.x proteins resulting in remarkably decreased INa and Ito. These data are consistent with a novel structural and functional association of INa and Ito in NRVMs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 45, Issue 3, September 2008, Pages 336-346
Journal: Journal of Molecular and Cellular Cardiology - Volume 45, Issue 3, September 2008, Pages 336-346
نویسندگان
Isabelle Deschênes, Antonis A. Armoundas, Steven P. Jones, Gordon F. Tomaselli,