Journal article
Physical and functional interaction between calcineurin and the cardiac L-type Ca2+ channel
Circulation research, Vol.105(1), pp.51-60
07/02/2009
DOI: 10.1161/CIRCRESAHA.109.199828
PMCID: PMC3038593
PMID: 19478199
Abstract
The L-type Ca(2+) channel (LTCC) is the major mediator of Ca(2+) influx in cardiomyocytes, leading to both mechanical contraction and activation of signaling cascades. Among these Ca(2+)-activated cascades is calcineurin, a protein phosphatase that promotes hypertrophic growth of the heart. Coimmunoprecipitations from heart extracts and pulldowns using heterologously expressed proteins provided evidence for direct binding of calcineurin at both the N and C termini of alpha(1)1.2. At the C terminus, calcineurin bound specifically at amino acids 1943 to 1971, adjacent to a well-characterized protein kinase (PK)A/PKC/PKG phospho-acceptor site Ser1928. In vitro assays demonstrated that calcineurin can dephosphorylate alpha(1)1.2. Channel function was increased in voltage-clamp recordings of I(Ca,L) from cultured cardiomyocytes expressing constitutively active calcineurin, consistent with previous observations in cardiac hypertrophy in vivo. Conversely, acute suppression of calcineurin pharmacologically or with specific peptides decreased I(Ca,L). These data reveal direct physical interaction between the LTCC and calcineurin in heart. Furthermore, they demonstrate that calcineurin induces robust increases in I(Ca,L) and highlight calcineurin as a key modulator of pathological electrical remodeling in cardiac hypertrophy.
Details
- Title: Subtitle
- Physical and functional interaction between calcineurin and the cardiac L-type Ca2+ channel
- Creators
- Samvit Tandan - Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75390-8573, USAYanggan WangThomas T WangNan JiangDuane D HallJohannes W HellXiang LuoBeverly A RothermelJoseph A Hill
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.105(1), pp.51-60
- DOI
- 10.1161/CIRCRESAHA.109.199828
- PMID
- 19478199
- PMCID
- PMC3038593
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Grant note
- HL-072016 / NHLBI NIH HHS NS035563 / NINDS NIH HHS R01 HL075173 / NHLBI NIH HHS R01 HL097768 / NHLBI NIH HHS P01 HL006296 / NHLBI NIH HHS R01 HL072016-07 / NHLBI NIH HHS HL-075173 / NHLBI NIH HHS HL-006296 / NHLBI NIH HHS R01 NS035563 / NINDS NIH HHS R01 HL072016 / NHLBI NIH HHS R01 HL080144 / NHLBI NIH HHS HL-080144 / NHLBI NIH HHS
- Language
- English
- Date published
- 07/02/2009
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094763302771
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