In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 109, No. suppl_1 ( 2011-12-09)
Abstract:
The source of Ca 2+ to hypertrophic signaling after myocardial infarction (MI) is not clearly defined. Transient Receptor Potential Canonical (TRPC) channels could be an important source of hypertrophic Ca 2+ after MI. The objective of this study was to determine if TRPC 4 is a major source of Ca 2+ influx mediating cardiac dysfunction after MI. Methods: Cardiac-specific transgenic mice that express a dominant-negative (dn) TRPC4 that reduces the activity of the TRPC1/4/5 subfamily of channels in the heart were used. MI was produced and in-vivo cardiac function was measured with ECHO. Myocytes were isolated and isoproterenol (ISO) effects on LTCC Current ( I Ca-L ), fractional shortening (FS) and Ca 2+ transients were measured 6 weeks after MI. Results: Baseline ejection fraction (EF) and fractional shortening (FS) were greater in (dn) TRPC4 vs. WT mice. Two weeks after MI, EF and FS were significantly decreased in all animals (WT: 37.1% and 18.2%; (dn) TRPC4: 41.7% and 20.5%), but there was no significant difference between WT and (dn) TRPC4 mice. Six weeks after MI, EF and FS were significant greater in (dn) TRPC4 compared with WT mice (WT: 37.4% and 18.2%; (dn) TRPC4: 52.2% and 27.4%). Heart weight and lung weight were significantly increased after 2 weeks MI, but there were significant lower heart and lung weight in (dn) TRPC4 vs. WT mice after 6 weeks MI. I Ca-L [[Unsupported Character - Codename & shy;]] after 6 weeks MI was smaller than that in sham myocytes, and there was no significant difference between (dn) TRPC4 and WT myocytes. Contractions and Ca 2+ transients were significantly greater in sham and post-MI (dn) TRPC4 vs. WT myocytes. ISO increased contractions and Ca 2+ transients to a similar extent in all myocytes. Conclusions: (dn) TRPC4 mice have greater baseline cardiac and myocyte function. While initial effects of MI were similar to control, there was improved function in these mice by 6 weeks. These results suggest that blocking TRPC4 after MI may reduce pathological cardiac remodeling.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.109.suppl_1.AP074
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2011
detail.hit.zdb_id:
1467838-X
