Journal article
The Cav3.2 T-Type Ca2+ Channel Is Required for Pressure Overload-Induced Cardiac Hypertrophy in Mice
Circulation research, Vol.104(4), pp.522-530
2009
DOI: 10.1161/CIRCRESAHA.108.184051
PMID: 19122177
Abstract
Voltage-gated T-type Ca2+ channels (T-channels) are normally expressed during embryonic development in ventricular myocytes but are undetectable in adult ventricular myocytes. Interestingly, T-channels are reexpressed in hypertrophied or failing hearts. It is unclear whether T-channels play a role in the pathogenesis of cardiomyopathy and what the mechanism might be. Here we show that the α1H voltage-gated T-type Ca2+ channel (Cav3.2) is involved in the pathogenesis of cardiac hypertrophy via the activation of calcineurin/nuclear factor of activated T cells (NFAT) pathway. Specifically, pressure overload–induced hypertrophy was severely suppressed in mice deficient for Cav3.2 (Cav3.2−/−) but not in mice deficient for Cav3.1 (Cav3.1−/−). Angiotensin II–induced cardiac hypertrophy was also suppressed in Cav3.2−/− mice. Consistent with these findings, cultured neonatal myocytes isolated from Cav3.2−/− mice fail to respond hypertrophic stimulation by treatment with angiotensin II. Together, these results demonstrate the importance of Cav3.2 in the development of cardiac hypertrophy both in vitro and in vivo. To test whether Cav3.2 mediates the hypertrophic response through the calcineurin/NFAT pathway, we generated Cav3.2−/−, NFAT-luciferase reporter mice and showed that NFAT-luciferase reporter activity failed to increase after pressure overload in the Cav3.2−/−/NFAT-Luc mice. Our results provide strong genetic evidence that Cav3.2 indeed plays a pivotal role in the induction of calcineurin/NFAT hypertrophic signaling and is crucial for the activation of pathological cardiac hypertrophy.
Details
- Title: Subtitle
- The Cav3.2 T-Type Ca2+ Channel Is Required for Pressure Overload-Induced Cardiac Hypertrophy in Mice
- Creators
- Chien-Sung CHIANG - Academia SinicaChing-Hui HUANG - Academia SinicaChien-Chang CHEN - Academia SinicaHockling CHIENG - Academia SinicaYa-Ting CHANG - Academia SinicaDory CHANG - Academia SinicaJi-Jr CHEN - Academia SinicaYong-Cyuan CHEN - Academia SinicaYen-Hui CHEN - Academia SinicaHee-Sup SHIN - Korea Institute of Science and TechnologyKevin P CAMPBELL - Department of Physiology and Biophysics and Department of Neurology Howard Hughes Medical Institute, University of Iowa, Iowa City, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.104(4), pp.522-530
- DOI
- 10.1161/CIRCRESAHA.108.184051
- PMID
- 19122177
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- Language
- English
- Date published
- 2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020884802771
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