Research output: Contribution to book/anthology/report/proceeding › Article in proceedings › Research › peer-review
The 1st to 3rd order branches of the mesenteric artery of anestisized Wistar rats were transfected with siRNAs targeting different exons of the α1C gene or with control non-related siRNAs. The effect of transfection was analyzed after 3 and 10 days using quantitative PCR and immunohistochemistry. The functional effects of transfection were studied using isometric myography.
Specific transfection downregulates mRNA of Cav1.2 by 93±2% within 3 days but the mRNA level recovered 10 days after transfection (110±13 % of the control level). Immunohistochemistry identified reduced Cav1.2 expression in the arteries transfected with siRNA directed against Cav1.2 α subunit. Surprisingly, normalized internal diameter of Cav1.2 downregulated arteries was significant reduced by 33±10% (n=7) vs. arteries transfected with non-related siRNA. The maximal force development to K+-depolarization was significantly reduced (by 72±10%, n=6). The responses to noradrenaline, vasopressin and caffeine were also suppressed in Cav1.2 downregulated arteries. The reduced force development was accompanied with reduced nifedipine sensitive [Ca2+]i increase. The responses to K+-depolarization and agonist-stimulation in arteries transfected with siRNA directed against α1C were upregulated in comparison with the controls 10 days after transfection. This upregulation was not, however, nifedipine-sensitive.
Using in vivo transfection of arteries with siRNA we demonstrated the importance of Cav1.2 for vascular structure and reactivity and its tight coupling with other cellular Ca2+ handling processes.Original language | English |
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Title of host publication | the Journal of Vascular Research |
Number of pages | 1 |
Publication year | 2008 |
Pages | 15 |
Publication status | Published - 2008 |
Event | 9TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES (ISRA) - HAMILTON ISLAND, Australia Duration: 17 Dec 2010 → … Conference number: 9 |
Conference | 9TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES (ISRA) |
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Nummer | 9 |
Land | Australia |
By | HAMILTON ISLAND |
Periode | 17/12/2010 → … |
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ID: 10325443