کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1945191 1053255 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Associated changes in HCN2 and HCN4 transcripts and If pacemaker current in myocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Associated changes in HCN2 and HCN4 transcripts and If pacemaker current in myocytes
چکیده انگلیسی

The time- and voltage-dependent inward current generated by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contributes to the tissue-specific rhythmic activities in the brain and heart. Four isoforms (HCN1–HCN4) have been identified. Previous studies showed that different HCN isoforms may form functional heteromeric channels. We report here that when HCN2 and HCN4 mRNA were injected into Xenopus oocytes with various ratios of HCN2 over HCN4 at 1:1, 10:1, and 1:10, respectively, the resultant channels showed a depolarized current activation and significantly faster activation kinetics near the midpoint of activation compared with HCN4 homomeric channels. In adult rat myocytes overexpressing HCN4, there was an associated increase in HCN2 mRNA. In neonatal rat myocytes in which HCN2 was knocked down, there was also a simultaneous decrease in HCN4 mRNA. Coimmunoprecipitation experiments showed that HCN2 and HCN4 channel proteins can associate with each other in adult rat ventricles. Finally, in adult myocytes overexpressing HCN4, the hyperpolarization-activated inward current activation, If, was shifted to physiological voltages from non-physiological voltages, associated with faster activation kinetics. These data suggested that different ratios of HCN2 and HCN4 transcripts overlapping in different tissues also contribute to the tissue-specific properties of If.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1788, Issue 5, May 2009, Pages 1138–1147
نویسندگان
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