ArticleProceedings of the National Academy of Sciences of the United States of America2008
Calmodulin-dependent gating of Ca(v)1.2 calcium channels in the absence of Ca(v)beta subunits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Reverse-engineered models reveal differential membrane properties of autonomic and cutaneous unmyelinated fibers.PLoS computational biology · 2024Article
- Regulation of Cardiac Cav1.2 Channels by Calmodulin.International journal of molecular sciences · 2023Review
- CaMolecular pharmacology · 2017Article
- α-Actinin Promotes Surface Localization and Current Density of the CaBiochemistry · 2017Article
- Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.Journal of molecular biology · 2013Article
- Competition between α-actinin and Ca²⁺-calmodulin controls surface retention of the L-type Ca²⁺ channel Ca(V)1.2.Neuron · 2013Article
- Cav1.2, cell proliferation, and new target in atherosclerosis.ISRN biochemistry · 2013Review
- Molecular Determinants of Cav1.2 Calcium Channel Inactivation.ISRN molecular biology · 2012Review
- Microdomain organization and frequency-dependence of CREB-dependent transcriptional signaling in heart cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2011Article
- RyRCa2+ leak limits cardiac Ca2+ window current overcoming the tonic effect of calmodulinin mice.PloS one · 2011Article
- Oligomerization of Cavbeta subunits is an essential correlate of Ca2+ channel activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Molecular determinants of the CaVbeta-induced plasma membrane targeting of the CaV1.2 channel.The Journal of biological chemistry · 2010Article
- Intra- and interdomain effects due to mutation of calcium-binding sites in calmodulin.The Journal of biological chemistry · 2010Article
- The Ca2+ channel subunit beta2 regulates Ca2+ channel abundance and function in inner hair cells and is required for hearing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- New Determinant for the CaVbeta2 subunit modulation of the CaV1.2 calcium channel.The Journal of biological chemistry · 2008Article
- Functional properties of the CaV1.2 calcium channel activated by calmodulin in the absence of alpha2delta subunits.Channels (Austin, Tex.)Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
It is generally accepted that to generate calcium currents in response to depolarization, Ca(v)1.2 calcium channels require association of the pore-forming alpha(1C) subunit with accessory Ca(v)beta and alpha(2)delta subunits. A single calmodulin (CaM) molecule is tethered to the C-terminal alpha(1C)-LA/IQ region and mediates Ca2+-dependent inactivation of the channel. Ca(v)beta subunits are stably associated with the alpha(1C)-interaction domain site of the cytoplasmic linker between internal repeats I and II and also interact dynamically, in a Ca2+-dependent manner, with the alpha(1C)-IQ region. Here, we describe a surprising discovery that coexpression of exogenous CaM (CaM(ex)) with alpha(1C)/alpha(2)delta in COS1 cells in the absence of Ca(v)beta subunits stimulates the plasma membrane targeting of alpha(1C), facilitates calcium channel gating, and supports Ca2+-dependent inactivation. Neither real-time PCR with primers complementary to monkey Ca(v)beta subunits nor coimmunoprecipitation analysis with exogenous alpha(1C) revealed an induction of endogenous Ca(v)beta subunits that could be linked to the effect of CaM(ex). Coexpression of a calcium-insensitive CaM mutant CaM(1234) also facilitated gating of Ca(v)beta-free Ca(v)1.2 channels but did not support Ca2+-dependent inactivation. Our results show there is a functional matchup between CaM(ex) and Ca(v)beta subunits that, in the absence of Ca(v)beta, renders Ca2+ channel gating facilitated by CaM molecules other than the one tethered to LA/IQ to support Ca2+-dependent inactivation. Thus, coexpression of CaM(ex) creates conditions when the channel gating, voltage- and Ca2+-dependent inactivation, and plasma-membrane targeting occur in the absence of Ca(v)beta. We suggest that CaM(ex) affects specific Ca(v)beta-free conformations of the channel that are not available to endogenous CaM.
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