ArticleThe Journal of biological chemistry2008
New Determinant for the CaVbeta2 subunit modulation of the CaV1.2 calcium channel.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Ahf-Caltide, a Novel Polypeptide Derived from Calpastatin, Protects against Oxidative Stress Injury by Stabilizing the Expression of CaInternational journal of molecular sciences · 2023Article
- Role of CaArchives of toxicology · 2023Review
- Association betweenBMJ open · 2018Article
- Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia.Channels (Austin, Tex.) · 2018Review
- Urotensin-II receptor stimulation of cardiac L-type Ca2+ channels requires the βγ subunits of Gi/o-protein and phosphatidylinositol 3-kinase-dependent protein kinase C β1 isoform.The Journal of biological chemistry · 2015Article
- Genetic modifiers to the PLN L39X mutation in a patient with DCM and sustained ventricular tachycardia?Global cardiology science & practice · 2015Article
- Molecular Determinants of Cav1.2 Calcium Channel Inactivation.ISRN molecular biology · 2012Review
- Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.Heart rhythm · 2010Article
- 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
- The ß subunit of voltage-gated Ca2+ channels.Physiological reviews · 2010Review
- Molecular determinants of the CaVbeta-induced plasma membrane targeting of the CaV1.2 channel.The Journal of biological chemistry · 2010Article
- CaMKII associates with CaV1.2 L-type calcium channels via selected beta subunits to enhance regulatory phosphorylation.Journal of neurochemistry · 2010Article
- Orientation of palmitoylated CaVbeta2a relative to CaV2.2 is critical for slow pathway modulation of N-type Ca2+ current by tachykinin receptor activation.The Journal of general physiology · 2009Article
- Genome-wide association study of blood pressure and hypertension.Nature genetics · 2009Article
- Effect of Ca(v)beta subunits on structural organization of Ca(v)1.2 calcium channels.PloS one · 2009Article
- Akt regulates L-type Ca2+ channel activity by modulating Cavalpha1 protein stability.The Journal of cell biology · 2009Article
- Calmodulin-dependent gating of Ca(v)1.2 calcium channels in the absence of Ca(v)beta subunits.Proceedings of the National Academy of Sciences of the United States of America · 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Ca(v)beta subunits support voltage gating of Ca(v)1.2 calcium channels and play important role in excitation-contraction coupling. The common central membrane-associated guanylate kinase (MAGUK) region of Ca(v)beta binds to the alpha-interaction domain (AID) and the IQ motif of the pore-forming alpha(1C) subunit, but these two interactions do not explain why the cardiac Ca(v)beta(2) subunit splice variants differentially modulate inactivation of Ca(2+) currents (I(Ca)). Previously we described beta(2Deltag), a functionally active splice variant of human Ca(v)beta(2) lacking MAGUK. By deletion analysis of beta(2Deltag), we have now identified a 41-amino acid C-terminal essential determinant (beta(2)CED) that stimulates I(Ca) in the absence of Ca(v)beta subunits and conveys a +20-mV shift in the peak of the I(Ca)-voltage relationship. The beta(2)CED is targeted by alpha(1C) to the plasma membrane, forms a complex with alpha(1C) but does not bind to AID. Electrophysiology and binding studies point to the calmodulin-interacting LA/IQ region in the alpha(1C) subunit C terminus as a functionally relevant beta(2)CED binding site. The beta(2)CED interacts with LA/IQ in a Ca(2+)- and calmodulin-independent manner and need LA, but not IQ, to activate the channel. Deletion/mutation analyses indicated that each of the three Ca(v)beta(2)/alpha(1C) interactions is sufficient to support I(Ca). However, beta(2)CED does not support Ca(2+)-dependent inactivation, suggesting that interactions of MAGUK with AID and IQ are crucial for Ca(2+)-induced inactivation. The beta(2)CED is conserved only in Ca(v)beta(2) subunits. Thus, beta(2)CED constitutes a previously unknown integrative part of the multifactorial mechanism of Ca(v)beta(2)-subunit differential modulation of the Ca(v)1.2 calcium channel that in beta(2Deltag) occurs without MAGUK.
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