Back to Search
Start Over
Cardiomyocyte-secreted acetylcholine is required for maintenance of homeostasis in the heart.
- Source :
- FASEB Journal; Dec2013, Vol. 27 Issue 12, p5072-5082, 11p
- Publication Year :
- 2013
-
Abstract
- Heart activity and long-term function are regulated by the sympathetic and parasympathetic branches of the nervous system. Parasympathetic neurons have received increased attention recently because acetylcholine (ACh) has been shown to play protective roles in heart disease. However, parasympathetic inner-vation is sparse in the heart, raising the question of how cholinergic signaling regulates cardiomyocytes. We hypothesized that non-neuronal secretion of ACh from cardiomyocytes plays a role in cholinergic regulation of cardiac activity. To test this possibility, we eliminated secretion of ACh exclusively from cardiomyocytes by targeting the vesicular acetylcholine transporter (VAChT). We find that lack of cardiomyocyte-secreted ACh disturbs the regulation of cardiac activity and causes cardiomyocyte remodeling. Mutant mice present normal hemodynamic parameters under nonstressful conditions; however, following exercise, their heart rate response is increased. Moreover, hearts from mutant mice present increased oxidative stress, altered calcium signaling, remodeling, and hypertrophy. Hence, without cardiomyocyte-derived ACh secretion, hearts from mutant mice show signs of imbalanced autonomic activity consistent with decreased cholinergic drive. These unexpected results suggest that cardiomyocyte-derived ACh is required for maintenance of cardiac homeostasis and regulates critical signaling pathways necessary to maintain normal heart activity. We propose that this non-neuronal source of ACh boosts parasympathetic cholinergic signaling to counterbalance sympathetic activity regulating multiple aspects of heart physiology. [ABSTRACT FROM AUTHOR]
- Subjects :
- HEART cells
CELLS
ACETYLCHOLINE
CHOLINE
HOMEOSTASIS
Subjects
Details
- Language :
- English
- ISSN :
- 08926638
- Volume :
- 27
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- FASEB Journal
- Publication Type :
- Academic Journal
- Accession number :
- 92701114
- Full Text :
- https://doi.org/10.1096/fj.13-238279