ArticleThe Journal of biological chemistry2012
Mutation of the calmodulin binding motif IQ of the L-type Ca(v)1.2 Ca2+ channel to EQ induces dilated cardiomyopathy and death.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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16 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- A Seven Amino Acid Long Region in the Cardiac CaCells · 2026Article
- Phenotypic expansion of CALM1/2-associated disorders to include neurologic phenotypes without arrhythmia.Human molecular genetics · 2026Article
- Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.Channels (Austin, Tex.) · 2025Review
- Cardiovascular inhalation for targeted drug delivery in cardiac disease.Heart failure reviews · 2025Review
- Mechanisms underlying dilated cardiomyopathy associated with FKBP12 deficiency.The Journal of general physiology · 2025Article
- Regulation of Cardiac Cav1.2 Channels by Calmodulin.International journal of molecular sciences · 2023Review
- Cardiac-Specific Expression of Cre Recombinase Leads to Age-Related Cardiac Dysfunction Associated with Tumor-like Growth of Atrial Cardiomyocyte and Ventricular Fibrosis and Ferroptosis.International journal of molecular sciences · 2023Article
- Hypochlorhydria reduces mortality in heart failure caused by Kcne2 gene deletion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Serotonin Disinhibits aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- "Getting Under the Hood" of Neuronal Signaling inJournal of experimental neuroscience · 2018Article
- An anti-PDGFRβ aptamer for selective delivery of small therapeutic peptide to cardiac cells.PloS one · 2018Article
- Article
- L-type CaWiley interdisciplinary reviews. Membrane transport and signaling · 2014Article
- Lobe-related concentration- and Ca(2+)-dependent interactions of calmodulin with C- and N-terminal tails of the CaV1.2 channel.The journal of physiological sciences : JPS · 2013Article
- L-type calcium channel targeting and local signalling in cardiac myocytes.Cardiovascular research · 2013Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiac excitation-contraction coupling (EC coupling) links the electrical excitation of the cell membrane to the mechanical contractile machinery of the heart. Calcium channels are major players of EC coupling and are regulated by voltage and Ca(2+)/calmodulin (CaM). CaM binds to the IQ motif located in the C terminus of the Ca(v)1.2 channel and induces Ca(2+)-dependent inactivation (CDI) and facilitation (CDF). Mutation of Ile to Glu (Ile1624Glu) in the IQ motif abolished regulation of the channel by CDI and CDF. Here, we addressed the physiological consequences of such a mutation in the heart. Murine hearts expressing the Ca(v)1.2(I1624E) mutation were generated in adult heterozygous mice through inactivation of the floxed WT Ca(v)1.2(L2) allele by tamoxifen-induced cardiac-specific activation of the MerCreMer Cre recombinase. Within 10 days after the first tamoxifen injection these mice developed dilated cardiomyopathy (DCM) accompanied by apoptosis of cardiac myocytes (CM) and fibrosis. In Ca(v)1.2(I1624E) hearts, the activity of phospho-CaM kinase II and phospho-MAPK was increased. CMs expressed reduced levels of Ca(v)1.2(I1624E) channel protein and I(Ca). The Ca(v)1.2(I1624E) channel showed "CDI" kinetics. Despite a lower sarcoplasmic reticulum Ca(2+) content, cellular contractility and global Ca(2+) transients remained unchanged because the EC coupling gain was up-regulated by an increased neuroendocrine activity. Treatment of mice with metoprolol and captopril reduced DCM in Ca(v)1.2(I1624E) hearts at day 10. We conclude that mutation of the IQ motif to IE leads to dilated cardiomyopathy and death.
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