Genomes and Genes
Gene Symbol: Cacna1c
Description: calcium voltage-gated channel subunit alpha1 C
Alias: RATIVS302, voltage-dependent L-type calcium channel subunit alpha-1C, L-type calcium channel alpha-1 subunit, RBC, brain class C, calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle, calcium channel, voltage-dependent, L type, alpha 1C subunit, calcium channel, voltage-dependent, alpha 1C subunit, voltage-gated calcium channel subunit alpha Cav1.2
- Schulla V, Renstrom E, Feil R, Feil S, Franklin I, Gjinovci A, et al. Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice. EMBO J. 2003;22:3844-54 pubmed..2 channel. Thus, the conduit of Ca(2+) entry determines the ability of the cation to elicit secretion. ..
- Maltez J, Nunziato D, Kim J, Pitt G. Essential Ca(V)beta modulatory properties are AID-independent. Nat Struct Mol Biol. 2005;12:372-7 pubmed
- Huber I, Wappl Kornherr E, Sinnegger Brauns M, Hoda J, Walter Bastl D, Striessnig J. Opposite effects of a single IIIS5 mutation on phenylalkylamine and dihydropyridine interaction with L-type Ca2+ channels. J Biol Chem. 2004;279:55211-7 pubmed..Mutation of Thr-1066 to a non-L-type tyrosine residue can be exploited to differentially affect phenylalkylamine and dihydropyridine binding to L-type Ca(2+) channels. ..
- Takahashi E, Fukuda K, Miyoshi S, Murata M, Kato T, Ita M, et al. Leukemia inhibitory factor activates cardiac L-Type Ca2+ channels via phosphorylation of serine 1829 in the rabbit Cav1.2 subunit. Circ Res. 2004;94:1242-8 pubmed..2 subunit via the actions of extracellular signal-regulated kinase and that this phosphorylation increases I(CaL) in cardiomyocytes. ..
- Golden K, Ren J, Dean A, Marsh J. Norepinephrine regulates the in vivo expression of the L-type calcium channel. Mol Cell Biochem. 2002;236:107-14 pubmed..01). We conclude norepinephrine treatment alters DHPr mRNA and protein levels, and augments excitation-contraction coupling, and thus may be important for modulating cardiac calcium homeostasis in vivo. ..
- Koch W, Ellinor P, Schwartz A. cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta. Evidence for the existence of alternatively spliced forms. J Biol Chem. 1990;265:17786-91 pubmed..6- and 12.0-kb mRNA species but not the 6.5-kb species. Southern analysis of rat genomic DNA reveals a low copy number of the gene encoding this type of calcium channel. ..
- Snutch T, Leonard J, Gilbert M, Lester H, Davidson N. Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci U S A. 1990;87:3391-5 pubmed..In the regions sequenced, the rat brain class C and D gene products share approximately 75% amino acid identity with the rabbit skeletal muscle Ca channel...
- Krizanova O, Varadi M, Schwartz A, Varadi G. Coexpression of skeletal muscle voltage-dependent calcium channel alpha 1 and beta cDNAs in mouse Ltk- cells increases the amount of alpha 1 protein in the cell membrane. Biochem Biophys Res Commun. 1995;211:921-7 pubmed..The data provide evidence that coexpression of alpha 1 and beta results in an increased amount of alpha 1 protein in the cell membrane. ..
- Tippens A, Pare J, Langwieser N, Moosmang S, Milner T, Smith Y, et al. Ultrastructural evidence for pre- and postsynaptic localization of Cav1.2 L-type Ca2+ channels in the rat hippocampus. J Comp Neurol. 2008;506:569-83 pubmed..These findings provide the first detailed ultrastructural analysis of Ca(v)1.2 localization in the brain and support functionally diverse roles of these channels in the hippocampal formation. ..
- Li R, Wang Y, Yang Z, He Y, Zhao T, Fan M, et al. Hypoxia-inducible factor-1Î± regulates the expression of L-type voltage-dependent Ca(2+) channels in PC12 cells under hypoxia. Cell Stress Chaperones. 2015;20:507-16 pubmed publisher..2 gene, but not that of the Cav1.3 gene. These data indicated that Cav1.2 might be regulated by HIF-1Î± as one of its downstream target genes and involved in regulation of PC12 cells death under hypoxia. ..
- Saada N, Carrillo E, Dai B, Wang W, Dettbarn C, Sanchez J, et al. Expression of multiple CaV1.2 transcripts in rat tissues mediated by different promoters. Cell Calcium. 2005;37:301-9 pubmed..Evidence in favor of still another promoter upstream of exon 2 has been uncovered. ..
- Varadi G, Mikala G, Lory P, Varadi M, Drouet B, Pincon Raymond M, et al. Endogenous cardiac Ca2+ channels do not overcome the E-C coupling defect in immortalized dysgenic muscle cells: evidence for a missing link. FEBS Lett. 1995;368:405-10 pubmed..The upregulation of the expression of alpha 1C results in functional Ca2+ channel activity, however, presumably not sufficient for excitation-contraction coupling. ..
- Schultz D, Mikala G, Yatani A, Engle D, Iles D, Segers B, et al. Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci U S A. 1993;90:6228-32 pubmed..The cloned alpha 1 subunit was expressed in Xenopus oocytes and single-channel analyses revealed native-like pharmacology and channel properties. ..
- Bernhem K, Krishnan K, Bondar A, Brismar H, Aperia A, Scott L. AT1-receptor response to non-saturating Ang-II concentrations is amplified by calcium channel blockers. BMC Cardiovasc Disord. 2017;17:126 pubmed publisher..Our findings have implications for the understanding of hyperactivity of the angiotensin system and for use of Ca2+ channel blockers as mono-therapy in hypertension. ..
- Uhrig S, Vandael D, Marcantoni A, Dedic N, Bilbao A, Vogt M, et al. Differential Roles for L-Type Calcium Channel Subtypes in Alcohol Dependence. Neuropsychopharmacology. 2017;42:1058-1069 pubmed publisher..2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1...
- Boczek N, Ye D, Jin F, Tester D, Huseby A, Bos J, et al. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals With Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death. Circ Arrhythm Electrophysiol. 2015;8:1122-32 pubmed publisher..Here, we identify a novel CACNA1C missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, ..
- Hall D, Feekes J, Arachchige Don A, Shi M, Hamid J, Chen L, et al. Binding of protein phosphatase 2A to the L-type calcium channel Cav1.2 next to Ser1928, its main PKA site, is critical for Ser1928 dephosphorylation. Biochemistry. 2006;45:3448-59 pubmed..2 is required for effective reversal of PKA-mediated channel phosphorylation. Accordingly, PKA as well as PP2A are constitutively associated with Ca(v)1.2 for its proper regulation by phosphorylation and dephosphorylation of serine 1928. ..
- Choi K, Chen J, Mitra S, Sarna S. Impaired integrity of DNA after recovery from inflammation causes persistent dysfunction of colonic smooth muscle. Gastroenterology. 2011;141:1293-301, 1301.e1-3 pubmed publisher..We investigated whether oxidative stress during inflammation impairs integrity of the promoter of Cacna1c, which encodes the pore-forming ?1C subunit of Ca(v)1.2b calcium channels...
- Catterall W. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3:a003947 pubmed publisher..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties. ..
- Wegener J, Schulla V, Koller A, Klugbauer N, Feil R, Hofmann F. Control of intestinal motility by the Ca(v)1.2 L-type calcium channel in mice. FASEB J. 2006;20:1260-2 pubmed..In conclusion, the Ca(v)1.2 channel is essential for electromechanical coupling and important for pharmaco-mechanical coupling in intestinal smooth muscle and cannot be substituted functionally by other Ca2+ entry pathways. ..
- Kraner S, Wang Q, Novak K, Cheng D, Cool D, Peng J, et al. Upregulation of the CaV 1.1-ryanodine receptor complex in a rat model of critical illness myopathy. Am J Physiol Regul Integr Comp Physiol. 2011;300:R1384-91 pubmed publisher..There was also selective degradation of myosin heavy chain relative to actin in CIM muscle. Taken together, our findings suggest that increased Ca(2+) release from the sarcoplasmic reticulum may contribute to pathology in CIM. ..
- Yang L, Liu G, Zakharov S, Bellinger A, Mongillo M, Marx S. Protein kinase G phosphorylates Cav1.2 alpha1c and beta2 subunits. Circ Res. 2007;101:465-74 pubmed..2 current was significantly reduced by coexpression of an alanine-substituted Ca(v)1.2 beta(2a) subunit (Ser(496)). Our results identify a molecular mechanism by which cGMP-PKG regulates Ca(v)1.2 phosphorylation and function. ..
- Yang D, Zhang S, Ge Y, Wang Y, Liu Y, Wu Z. [Effect on expression of vascular smooth muscle cell calcium channel in rats exposed in low temperature]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2011;29:224-6 pubmed..86, P < 0.01). Repeated cold exposure can establish cold-induced hypertension, and the level of vascular smooth muscle cells LTCC?1C expression increase. ..
- Splawski I, Timothy K, Sharpe L, Decher N, Kumar P, Bloise R, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119:19-31 pubmed..These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism. ..
- LichvÃ¡rovÃ¡ L, LacinovÃ¡ Ä. Ca(V)1.2 and Ca(V)1.3 L-type calcium channels regulate the resting membrane potential but not the expression of calcium transporters in differentiated PC12 cells. Gen Physiol Biophys. 2015;34:157-65 pubmed publisher..of LTCC subtypes was downregulated by transfection of NGF-differentiated PC12 cells with siRNA for either CACNA1C or CACNA1D gene. Efficiency of gene silencing was verified by RT-PCR and by functional essay...
- Tezuka N, Ali M, Chwalisz K, Garfield R. Changes in transcripts encoding calcium channel subunits of rat myometrium during pregnancy. Am J Physiol. 1995;269:C1008-17 pubmed..Progesterone withdrawal or blockade appears to be responsible for regulating levels of mRNA for VDCC in the myometrium in preparation for labor...
- Leroy J, Abi Gerges A, Nikolaev V, Richter W, Lechêne P, Mazet J, et al. Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases. Circ Res. 2008;102:1091-100 pubmed publisher..These results reveal temporally distinct beta-adrenergic receptor cAMP compartments in ARVMs and shed new light on the intricate roles of PDE3 and PDE4. ..
- Peng S, Hajela R, Atchison W. Effects of methylmercury on human neuronal L-type calcium channels transiently expressed in human embryonic kidney cells (HEK-293). J Pharmacol Exp Ther. 2002;302:424-32 pubmed..Furthermore, DHP agonists and antagonists retain their ability to affect L-type Ca(2+) channel current even in the presence of MeHg. ..
- Fan Q, Vanderpool K, Marsh J. A 27 bp cis-acting sequence is essential for L-type calcium channel alpha(1C) subunit expression in vascular smooth muscle cells. Biochim Biophys Acta. 2002;1577:401-11 pubmed..We conclude that there is a 27 bp region in the promoter of the Ca(v)1.2 gene to which nuclear proteins from VSMC bind and strongly regulate the basal promoter activity. ..
- Cens T, Rousset M, Kajava A, Charnet P. Molecular determinant for specific Ca/Ba selectivity profiles of low and high threshold Ca2+ channels. J Gen Physiol. 2007;130:415-25 pubmed..These data therefore attribute to the DCS a unique role in the specific shaping of the Ca(2+) influx between the different HVA channels...
- Haase H, Alvarez J, Petzhold D, Doller A, Behlke J, Erdmann J, et al. Ahnak is critical for cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation. FASEB J. 2005;19:1969-77 pubmed..This genetic ahnak variant might cause individual differences in I(CaL) regulation upon physiological challenges or therapeutic interventions. ..
- Ji L, Tong L, Peng J, Jin X, Wei D, Xu B, et al. Changes in the expression of the vitamin D receptor and LVSCC?A1C in the rat hippocampus submitted to single prolonged stress. Mol Med Rep. 2014;9:1165-70 pubmed publisher..These results indicated that VDR may be involved in the pathogenesis of SPS rats, thereby providing an alternative preparation to search for optimal therapeutic strategies for PTSD. ..
- Qian A, Song D, Li Y, Liu X, Tang D, Yao W, et al. Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid. Mol Pain. 2013;9:15 pubmed publisher..We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity...
- Wegener J, Schulla V, Lee T, Koller A, Feil S, Feil R, et al. An essential role of Cav1.2 L-type calcium channel for urinary bladder function. FASEB J. 2004;18:1159-61 pubmed..These results show that the Cav1.2 Ca2+ channel is essential for normal bladder function. The Rho-kinase and Ca2+-release pathways cannot compensate the lack of the L-type Ca2+ channel. ..
- Zhao Y, Xu J, Gong J, Qian L. L-type calcium channel current up-regulation by chronic stress is associated with increased alpha(1c) subunit expression in rat ventricular myocytes. Cell Stress Chaperones. 2009;14:33-41 pubmed publisher..Thus, it would provide a new insight into the mechanism of cardiomyocyte injury induced by stress. ..
- Avila G, Medina I, Jiménez E, Elizondo G, Aguilar C. Transforming growth factor-beta1 decreases cardiac muscle L-type Ca2+ current and charge movement by acting on the Cav1.2 mRNA. Am J Physiol Heart Circ Physiol. 2007;292:H622-31 pubmed..Instead, we found that TGF-beta1 decreases the expression levels of atrial Ca(V)1.2 mRNA (70%). Thus TGF-beta1 downregulates atrial L-channel expression and may be therefore contributing to the in vivo cardiac electrical remodeling. ..
- Tang Z, Liao P, Li G, Jiang F, Yu D, Hong X, et al. Differential splicing patterns of L-type calcium channel Cav1.2 subunit in hearts of Spontaneously Hypertensive Rats and Wistar Kyoto Rats. Biochim Biophys Acta. 2008;1783:118-30 pubmed..2 transcripts identified in SHR hearts provide a different and new perspective in understanding the possible role of molecular remodeling of Cav1.2 channels in cardiac hypertrophy as a consequence of hypertension. ..
- Cheng X, Liu J, Asuncion Chin M, Blaskova E, Bannister J, Dopico A, et al. A novel Ca(V)1.2 N terminus expressed in smooth muscle cells of resistance size arteries modifies channel regulation by auxiliary subunits. J Biol Chem. 2007;282:29211-21 pubmed..novel, cysteine rich N terminus that is derived from exon 1 (termed "exon 1c"), which is located within CACNA1C, the Ca(V)1.2 gene...
- Tandan S, Wang Y, Wang T, Jiang N, Hall D, Hell J, et al. Physical and functional interaction between calcineurin and the cardiac L-type Ca2+ channel. Circ Res. 2009;105:51-60 pubmed publisher..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. ..
- Wang Y, Deng X, Mancarella S, Hendron E, Eguchi S, Soboloff J, et al. The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels. Science. 2010;330:105-9 pubmed publisher..Such coordinated control of the widely expressed Ca(V)1.2 and Orai channels has major implications for Ca(2+) signal generation in excitable and nonexcitable cells. ..
- Walsh C, Davies A, Butcher A, Dolphin A, Kitmitto A. Three-dimensional structure of CaV3.1: comparison with the cardiac L-type voltage-gated calcium channel monomer architecture. J Biol Chem. 2009;284:22310-21 pubmed publisher..2 binding and for the first time identifies the size and organization of the alpha2delta polypeptides. ..
- Li W, Zheng N, Yuan Q, Xu K, Yang F, Gu L, et al. NFAT5-mediated CACNA1C expression is critical for cardiac electrophysiological development and maturation. J Mol Med (Berl). 2016;94:993-1002 pubmed publisherEntry of calcium into cardiomyocyte via L-type calcium channel (LTCC) is fundamental to cardiac contraction. CACNA1C, a type of LTCC and a hallmark of a matured ventricular myocyte, is developmentally regulated...
- Jiao G, Hao L, Gao C, Chen L, Sun X, Yang H, et al. Reduced DHPR?1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis. Muscle Nerve. 2013;48:745-51 pubmed publisher..Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPR?1s and RyR1, the isoforms of skeletal muscles. ..
- Nitert M, Nagorny C, Wendt A, Eliasson L, Mulder H. CaV1.2 rather than CaV1.3 is coupled to glucose-stimulated insulin secretion in INS-1 832/13 cells. J Mol Endocrinol. 2008;41:1-11 pubmed publisher..2 expression in transfected cells since knock-down of Ca(V)1.3 did not affect glucose-stimulated insulin secretion. In summary, our results suggest that Ca(V)1.2 is critical for insulin secretion in INS-1 832/13 cells. ..
- Splawski I, Timothy K, Decher N, Kumar P, Sachse F, Beggs A, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A. 2005;102:8089-96; discussion 8086-8 pubmed..These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS. ..
- Ma W, Holz R, Uhler M. Expression of a cDNA for a neuronal calcium channel alpha 1 subunit enhances secretion from adrenal chromaffin cells. J Biol Chem. 1992;267:22728-32 pubmed..All the cDNA clones reported here showed high homology to the rat brain class C cDNA sequence (Snutch, T. P., Tomlinson, W. J., Leonard, J. P., and Gilbert, M. M. (1991) Neuron 7, 45-57)...
- Braunstein T, Inoue R, Cribbs L, Oike M, Ito Y, Holstein Rathlou N, et al. The role of L- and T-type calcium channels in local and remote calcium responses in rat mesenteric terminal arterioles. J Vasc Res. 2009;46:138-51 pubmed publisher..Both L- and T-type channels mediate Ca(2+) entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se. ..
- Maturana A, Walchli S, Iwata M, Ryser S, Van Lint J, Hoshijima M, et al. Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel. Cardiovasc Res. 2008;78:458-65 pubmed publisher..We propose a model where ENH1 scaffolds PKD1 to alpha1C in order to form a signalling complex that regulates the activity of cardiac L-type voltage-gated Ca(2+) channels. ..
- Park C, Shcheglovitov A, Dolmetsch R. The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channels. Science. 2010;330:101-5 pubmed publisher..This establishes a previously unknown function for STIM1 and provides a molecular mechanism to explain the reciprocal regulation of these two channels in cells. ..
- Scriven D, Dan P, Moore E. Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes. Biophys J. 2000;79:2682-91 pubmed..We conclude that if either the slip mode conductance of the Na(+) channel or the reverse mode of the Na(+)/Ca(2+) exchanger are to contribute to the contractile force, the fuzzy space must extend outside of the dyad. ..
- Coppola T, Magnin Luthi S, Perret Menoud V, Gattesco S, Schiavo G, Regazzi R. Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. J Biol Chem. 2001;276:32756-62 pubmed..We propose that the Rab3 effector RIM is a scaffold protein that participates through its multiple binding partners in the docking and fusion of secretory vesicles at the release sites. ..