ArticleCirculation research2009
L-type calcium channel C terminus autoregulates transcription.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- C-Terminus of CaCells · 2026Article
- Sudden death-associated KCNH2 variants exert opposing effects on a nuclear subdomain of the cardiac potassium channel hERG1.The Journal of biological chemistry · 2026Article
- Sudden Death-AssociatedbioRxiv : the preprint server for biology · 2025Article
- Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.NPJ Regenerative medicine · 2025Article
- Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac CaBMC biology · 2024Article
- Opto-chemogenetic inhibition of L-type CaCell reports methods · 2024Article
- Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity.Research square · 2023Article
- The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023Review
- Disruption of mitochondrial and lysosomal functions by humanFrontiers in molecular neuroscience · 2023Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Cytosolic peptides encoding CaCommunications biology · 2022Article
- Adrenergic Regulation of Calcium Channels in the Heart.Annual review of physiology · 2022Review
- Adult spiny mice (Acomys) exhibit endogenous cardiac recovery in response to myocardial infarction.NPJ Regenerative medicine · 2021Article
- Reconstitution of β-adrenergic regulation of CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Sodium channel β1 subunits participate in regulated intramembrane proteolysis-excitation coupling.JCI insight · 2021Article
- CaCells · 2020Article
- Myocardial Dysfunction after Severe Food Restriction Is Linked to Changes in the Calcium-Handling Properties in Rats.Nutrients · 2019Article
- The Role of 17β-Estradiol and Estrogen Receptors in Regulation of CaFrontiers in endocrinology · 2019Review
- The effect of intrauterine growth restriction on CaPhysiological reports · 2018Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Calcium homeostasis is critical for cardiac myocyte function and must be tightly regulated. The guiding hypothesis of this study is that a carboxyl-terminal cleavage product of the cardiac L-type calcium channel (Ca(V)1.2) autoregulates expression. First, we confirmed that the Ca(V)1.2 C terminus (CCt) is cleaved in murine cardiac myocytes from mature and developing ventricle. Overexpression of full-length CCt caused a 34+/-8% decrease of Ca(V)1.2 promoter activity, and truncated CCt caused an 80+/-3% decrease of Ca(V)1.2 promoter (n=12). The full-length CCt distributes into cytosol and nucleus. A deletion mutant of CCt has a greater relative affinity for the nucleus than full-length CCt, and this is consistent with increased repression of Ca(V)1.2 promoter activity by truncated CCt. Chromatin immunoprecipitation analysis revealed that CCt interacts with the Ca(V)1.2 promoter in adult ventricular cardiac myocytes at promoter modules containing Nkx2.5/Mef2, C/EBp, and a cis regulatory module. The next hypothesis tested was that CCt contributes to transcriptional signaling associated with cellular hypertrophy. We explored whether fetal cardiac myocyte Ca(V)1.2 was regulated by serum in vitro. We tested atrial natriuretic factor promoter activity as a positive control and measured the serum response of Ca(V)1.2 promoter, protein, and L-type current (I(Ca,L)) from fetal mouse ventricular myocytes. Serum increased atrial natriuretic factor promoter activity and cell size as expected. Serum withdrawal increased Ca(V)1.2 promoter activity, mRNA, and I(Ca,L). Moreover, serum withdrawal decreased the relative nuclear localization of CCt. A combination of promoter deletion mutant analyses, and the response of promoter mutants to serum withdrawal support the conclusion that CCt, a proteolytic fragment of Ca(V)1.2, autoregulates Ca(V)1.2 expression in cardiac myocytes. These data support the novel mechanism that a mobile segment of Ca(V)1.2 links Ca handling to nuclear signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.