Gene Symbol: Cacna1c
Description: calcium channel, voltage-dependent, L type, alpha 1C subunit
Alias: Cav1.2, Cchl1a1, D930026N18Rik, MBC, MELC-CC, voltage-dependent L-type calcium channel subunit alpha-1C, brain class C, calcium channel voltage-dependent alpha1c subunit, calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle, neuronal voltage-gated calcium channel alpha 1C subunit, skeletal muscle-specific calcium channel, voltage-gated calcium channel subunit alpha Cav1.2
Species: mouse
Products:     Cacna1c

Top Publications

  1. Tang Z, Zheng S, Nikolic J, Black D. Developmental control of CaV1.2 L-type calcium channel splicing by Fox proteins. Mol Cell Biol. 2009;29:4757-65 pubmed publisher
    ..These results demonstrate that the Fox protein family is playing a key role in tuning the properties of CaV1.2 calcium channels during neuronal development. ..
  2. Seisenberger C, Specht V, Welling A, Platzer J, Pfeifer A, Kühbandner S, et al. Functional embryonic cardiomyocytes after disruption of the L-type alpha1C (Cav1.2) calcium channel gene in the mouse. J Biol Chem. 2000;275:39193-9 pubmed
    ..3) knockout embryos at day 12.5 p.c. These results indicate that, up to day 14 p.c., contraction of murine embryonic hearts requires an unidentified, low affinity L-type like calcium channel. ..
  3. 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. ..
  4. Rougier J, Albesa M, Abriel H, Viard P. Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) controls the sorting of newly synthesized Ca(V)1.2 calcium channels. J Biol Chem. 2011;286:8829-38 pubmed publisher
    ..Altogether, our results suggest that Nedd4-1 interferes with the chaperon role of Ca(v)? at the endoplasmic reticulum/Golgi level to prevent the delivery of Ca(v) channels at the plasma membrane. ..
  5. Altier C, Garcia Caballero A, Simms B, You H, Chen L, Walcher J, et al. The Cav? subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. Nat Neurosci. 2011;14:173-80 pubmed publisher
    ..Thus, Cav?? regulates the ubiquitination and stability of the calcium channel complex. ..
  6. Cui J, Zhong R, Chu E, Zhang X, Zhang W, Fang C, et al. Correlation between oxidative stress and L-type calcium channel expression in the ventricular myocardia of selenium-deficient mice. J Int Med Res. 2012;40:1677-87 pubmed
    Expression of the Cacna1c (calcium channel, voltage-dependent, L-type, ?1C subunit) gene was studied to investigate the relationship between oxidative stress and L-type calcium channels in the myocardium of selenium-deficient mice...
  7. Bader P, Faizi M, Kim L, Owen S, Tadross M, Alfa R, et al. Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci U S A. 2011;108:15432-7 pubmed publisher
    ..Our results suggest that when TS mutant channels are expressed at levels low enough to avoid fatality, they are sufficient to cause multiple, distinct behavioral abnormalities, in line with the core aspects of ASD...
  8. Ronkainen J, Hänninen S, Korhonen T, Koivumäki J, Skoumal R, Rautio S, et al. Ca2+-calmodulin-dependent protein kinase II represses cardiac transcription of the L-type calcium channel alpha(1C)-subunit gene (Cacna1c) by DREAM translocation. J Physiol. 2011;589:2669-86 pubmed publisher
    ..The effect of CaMKII on the ?1C-subunit gene (Cacna1c) promoter was abolished by deletion of the downstream regulatory element (DRE), which binds transcriptional ..
  9. Sinnegger Brauns M, Hetzenauer A, Huber I, Renstrom E, Wietzorrek G, Berjukov S, et al. Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. J Clin Invest. 2004;113:1430-9 pubmed
    ..This animal model provides a useful tool to elucidate whether Ca(v)1.3-selective channel modulation represents a novel pharmacological approach to modify CNS function without major peripheral effects. ..

More Information


  1. Yang L, Wang Z, Wang B, Justice N, Zheng H. Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity. J Neurosci. 2009;29:15660-8 pubmed publisher
    ..2. These results provide a direct link between APP and calcium signaling and might help explain how altered APP regulation leads to changes in synaptic function that occur with AD. ..
  2. 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. ..
  3. Shao Y, Czymmek K, Jones P, Fomin V, Akanbi K, Duncan R, et al. Dynamic interactions between L-type voltage-sensitive calcium channel Cav1.2 subunits and ahnak in osteoblastic cells. Am J Physiol Cell Physiol. 2009;296:C1067-78 pubmed publisher
    ..Collectively, we showed that Ca(v)1.2 and beta(2)-subunits and ahnak form a stable complex in osteoblastic cells that permits Ca(2+) signaling independently of association with the actin cytoskeleton. ..
  4. Koczor C, Fields E, Jedrzejczak M, Jiao Z, Ludaway T, Russ R, et al. Methamphetamine and HIV-Tat alter murine cardiac DNA methylation and gene expression. Toxicol Appl Pharmacol. 2015;288:409-19 pubmed publisher
    ..Among those, only the promoter for CACNA1C that encodes L-type calcium channel Cav1...
  5. Hall D, Davare M, Shi M, Allen M, Weisenhaus M, McKnight G, et al. Critical role of cAMP-dependent protein kinase anchoring to the L-type calcium channel Cav1.2 via A-kinase anchor protein 150 in neurons. Biochemistry. 2007;46:1635-46 pubmed
    ..These results demonstrate the physiological relevance of PKA anchoring by AKAPs in general and AKAP150 specifically in the regulation of Cav1.2 in vivo. ..
  6. Bodrikov V, Sytnyk V, Leshchyns ka I, den Hertog J, Schachner M. NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its catalytic activity and neurite outgrowth. J Cell Biol. 2008;182:1185-200 pubmed publisher
    ..Thus, we reveal a novel function for a cell adhesion molecule in coordination of cell behavior with intracellular phosphatase activity. ..
  7. Link S, Meissner M, Held B, Beck A, Weissgerber P, Freichel M, et al. Diversity and developmental expression of L-type calcium channel beta2 proteins and their influence on calcium current in murine heart. J Biol Chem. 2009;284:30129-37 pubmed publisher
  8. Swift F, Franzini Armstrong C, Øyehaug L, Enger U, Andersson K, Christensen G, et al. Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule remodeling after Serca2 knockout. Proc Natl Acad Sci U S A. 2012;109:3997-4001 pubmed publisher
    ..T-tubule proliferation occurs without loss of the original ordered transverse orientation and thus constitutes the basis for compensation of the declining SR function without structural disarrangement...
  9. Yucel G, Altindag B, Gomez Ospina N, Rana A, Panagiotakos G, Lara M, et al. State-dependent signaling by Cav1.2 regulates hair follicle stem cell function. Genes Dev. 2013;27:1217-22 pubmed publisher
    ..Our findings show how channels act in nonexcitable tissues to regulate stem cells and may lead to novel therapeutics for tissue regeneration...
  10. Chaudhari N. A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice. J Biol Chem. 1992;267:25636-9 pubmed
    ..It is possible that premature termination of translation renders the mutant mRNA subject to degradation by nucleases. This work resolves a long-standing controversy on the nature of the primary genetic defect in muscular dysgenesis. ..
  11. Ding J, Domes K, Hofmann F, Wegener J. Truncation of murine CaV1.2 at Asp 1904 increases CaV1.3 expression in embryonic atrial cardiomyocytes. Pflugers Arch. 2013;465:955-64 pubmed publisher
    ..3 protein in the Stop/Stop atrium. We suggest that, in contrast to Stop/Stop ventricular CMs, Stop/Stop atrial CMs can compensate the functional loss of the truncated CaV1.2 channel with an upregulation of the CaV1.3 channel. ..
  12. Shi J, Gu P, Zhu Z, Liu J, Chen Z, Sun X, et al. Protein phosphatase 2A effectively modulates basal L-type Ca(2+) current by dephosphorylating Ca(v)1.2 at serine 1866 in mouse cardiac myocytes. Biochem Biophys Res Commun. 2012;418:792-8 pubmed publisher
    ..2 in cardiac-specific PP2A C? knockout mice. These phenomena were reproduced by treatment with okadaic acid, a PP2A inhibitor, in H9c2 cells. In summary, our data reveal the functional role of PP2A in cardiac Ca(v)1.2 regulation. ..
  13. Ma Y, Kobrinsky E, Marks A. Cloning and expression of a novel truncated calcium channel from non-excitable cells. J Biol Chem. 1995;270:483-93 pubmed
    ..A MELC calcium channel/cardiac DHPR chimera, co-expressed with the alpha 2 and beta subunits of the DHPR, forms a functional calcium channel in Xenopus oocytes. ..
  14. Schmutz I, Chavan R, Ripperger J, Maywood E, Langwieser N, Jurik A, et al. A specific role for the REV-ERBα-controlled L-Type Voltage-Gated Calcium Channel CaV1.2 in resetting the circadian clock in the late night. J Biol Rhythms. 2014;29:288-98 pubmed publisher
    ..To parse out the distinct roles of the L-type VGCCs, we analyzed mice deficient in Cav1.2 (Cacna1c) in brain tissue. We found that mice deficient in the Cav1...
  15. Koppe G, Mallien A, Berger S, Bartsch D, Gass P, Vollmayr B, et al. CACNA1C gene regulates behavioral strategies in operant rule learning. PLoS Biol. 2017;15:e2000936 pubmed publisher
    ..2 channels and the CACNA1C gene have been associated with severe learning deficits and psychiatric disorders...
  16. Pedrozo Z, Criollo A, Battiprolu P, Morales C, Contreras Ferrat A, Fernández C, et al. Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability. Circulation. 2015;131:2131-42 pubmed publisher
  17. Tyser R, Miranda A, Chen C, Davidson S, Srinivas S, Riley P. Calcium handling precedes cardiac differentiation to initiate the first heartbeat. elife. 2016;5: pubmed publisher
    ..NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation. ..
  18. Wegener J, Loga F, Stegner D, Nieswandt B, Hofmann F. Phospholipase D1 is involved in ?1-adrenergic contraction of murine vascular smooth muscle. FASEB J. 2014;28:1044-8 pubmed publisher
    ..2(-/-) mice) but still present in the heterozygous control mice. ?1-Adrenergic contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the ?1-adrenergic-induced CaV1.2 channel activity. ..
  19. Goonasekera S, Hammer K, Auger Messier M, Bodi I, Chen X, Zhang H, et al. Decreased cardiac L-type Ca²? channel activity induces hypertrophy and heart failure in mice. J Clin Invest. 2012;122:280-90 pubmed publisher
    ..for the gene encoding the pore-forming subunit of LTCC (calcium channel, voltage-dependent, L type, ?1C subunit [Cacna1c mice; referred to herein as ?1C?/? mice]) and mice in which this gene was loxP targeted to achieve graded heart-..
  20. Kumar D, Dedic N, Flachskamm C, Voulé S, Deussing J, Kimura M. Cacna1c (Cav1.2) Modulates Electroencephalographic Rhythm and Rapid Eye Movement Sleep Recovery. Sleep. 2015;38:1371-80 pubmed publisher
    The CACNA1C gene encodes the alpha 1C (α1C) subunit of the Cav1.2 voltage-dependent L-type calcium channel (LTCC). Some of the other voltage-dependent calcium channels, e.g., P-/Q-type, Cav2.1; N-type, Cav2.2; E-/R-type, Cav2...
  21. Qian H, Patriarchi T, Price J, Matt L, Lee B, Nieves Cintrón M, et al. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the ?2-adrenergic receptor in neurons. Sci Signal. 2017;10: pubmed publisher
    ..2 and enhancement of its activity by the ?2-adrenergic receptor (?2AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Cav1.2 by PKA in cardiomyocytes and hippocampal neurons. ..
  22. Cobine C, Hannah E, Zhu M, Lyle H, Rock J, Sanders K, et al. ANO1 in intramuscular interstitial cells of Cajal plays a key role in the generation of slow waves and tone in the internal anal sphincter. J Physiol. 2017;595:2021-2041 pubmed publisher
    ..ANO1, encoded by Ano1) and voltage-dependent L-type Ca2+ channels (CavL , encoded by Cacna1c)...
  23. 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. ..
  24. Shao Y, Alicknavitch M, Farach Carson M. Expression of voltage sensitive calcium channel (VSCC) L-type Cav1.2 (alpha1C) and T-type Cav3.2 (alpha1H) subunits during mouse bone development. Dev Dyn. 2005;234:54-62 pubmed
    ..We conclude that both L-type Ca(v)1.2 (alpha(1C)) and T-type Ca(v)3.2 (alpha(1H)) VSCCs are dynamically regulated in bones and cartilages during endochondral bone development. ..
  25. Schlick B, Flucher B, Obermair G. Voltage-activated calcium channel expression profiles in mouse brain and cultured hippocampal neurons. Neuroscience. 2010;167:786-98 pubmed publisher
    ..Developmental changes are likely determined by an intrinsic program and not regulated by changes in neuronal activity. ..
  26. 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. ..
  27. Jaleel N, Nakayama H, Chen X, Kubo H, MacDonnell S, Zhang H, et al. Ca2+ influx through T- and L-type Ca2+ channels have different effects on myocyte contractility and induce unique cardiac phenotypes. Circ Res. 2008;103:1109-19 pubmed publisher
  28. 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. ..
  29. Toba Y, Pakiam J, Wray S. Voltage-gated calcium channels in developing GnRH-1 neuronal system in the mouse. Eur J Neurosci. 2005;22:79-92 pubmed
    ..These results indicate that extracellular calcium is required for initiating GnRH-1 neuronal migration and that these events are partially dependent on N-type VGCC signals. ..
  30. Wang S, Stanika R, Wang X, Hagen J, Kennedy M, Obermair G, et al. Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated Cav1.2 Ca2+ Channels at Excitatory Synapses. J Neurosci. 2017;37:4679-4691 pubmed publisher
    ..This interaction promotes coupling of Cav1.2 channels to activity-dependent gene transcription. Our results reveal a mechanism that may contribute to the roles of Cav1.2 in regulating cognition and mood. ..
  31. Leroy J, Richter W, Mika D, Castro L, Abi Gerges A, Xie M, et al. Phosphodiesterase 4B in the cardiac L-type Ca²? channel complex regulates Ca²? current and protects against ventricular arrhythmias in mice. J Clin Invest. 2011;121:2651-61 pubmed publisher
    ..These results identify PDE4B in the CaV1.2 complex as a critical regulator of ICa,L during ?-AR stimulation and suggest that distinct PDE4 subtypes are important for normal regulation of Ca²?-induced Ca²? release in cardiomyocytes. ..
  32. Cheli V, Santiago González D, Spreuer V, Paez P. Voltage-gated Ca2+ entry promotes oligodendrocyte progenitor cell maturation and myelination in vitro. Exp Neurol. 2015;265:69-83 pubmed publisher
    ..Together, this set of in vitro experiments characterizes the involvement of L-type VOCCs on OPC maturation as well as the role played by these Ca(++) channels during the early phases of myelination. ..
  33. GAMELLI A, McKinney B, White J, Murphy G. Deletion of the L-type calcium channel Ca(V) 1.3 but not Ca(V) 1.2 results in a diminished sAHP in mouse CA1 pyramidal neurons. Hippocampus. 2011;21:133-41 pubmed publisher
    ..3 in the slow AHP (sAHP). Thus, the results of our study demonstrate that deletion of Ca(V) 1.3, but not Ca(V) 1.2, significantly impacts the generation of the sAHP. ..
  34. Vergnes L, Phan J, Stolz A, Reue K. A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13. J Lipid Res. 2003;44:503-11 pubmed
    ..Our findings dramatically expand the repertoire of AKR genes and identify unrecognized family members with potential roles in the regulation of steroid metabolism. ..
  35. El Khoury N, Mathieu S, Fiset C. Interleukin-1? reduces L-type Ca2+ current through protein kinase C? activation in mouse heart. J Biol Chem. 2014;289:21896-908 pubmed publisher
    ..These effects implicated ROS signaling and PKC? activation. These findings could contribute to explain the role of IL-1? in the development of arrhythmia and heart failure. ..
  36. Fu Y, Westenbroek R, Scheuer T, Catterall W. Basal and β-adrenergic regulation of the cardiac calcium channel CaV1.2 requires phosphorylation of serine 1700. Proc Natl Acad Sci U S A. 2014;111:16598-603 pubmed publisher
    ..As a consequence, blocking PKA phosphorylation at this site impairs cardiovascular physiology in vivo, leading to reduced exercise capacity in the fight-or-flight response and development of cardiac hypertrophy. ..
  37. Crump S, Correll R, Schroder E, Lester W, Finlin B, Andres D, et al. L-type calcium channel alpha-subunit and protein kinase inhibitors modulate Rem-mediated regulation of current. Am J Physiol Heart Circ Physiol. 2006;291:H1959-71 pubmed
    ..We conclude that Rem is capable of regulating L-type current, that release of Rem block is modulated by cellular kinase pathways, and that the Ca(V)1.2 COOH terminus contributes to Rem-dependent channel inhibition. ..
  38. Liu Y, Harding M, Pittman A, Dore J, Striessnig J, Rajadhyaksha A, et al. Cav1.2 and Cav1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area. J Neurophysiol. 2014;112:1119-30 pubmed publisher
    ..3(-/-) mice. These results indicate that the Cav1.3 subtype is crucial to regulation of basal single-spike firing, while activation of both Cav1.2 and Cav1.3 can support burst firing of VTA neurons. ..
  39. Hasreiter J, Goldnagl L, Böhm S, Kubista H. Cav1.2 and Cav1.3 L-type calcium channels operate in a similar voltage range but show different coupling to Ca(2+)-dependent conductances in hippocampal neurons. Am J Physiol Cell Physiol. 2014;306:C1200-13 pubmed publisher
    ..Moreover, our findings suggest that Cav1.3 knockout mice together with Cav1.2DHP(-)-knockin mice provide valuable models for future investigation of hippocampal LTCC-dependent afterdepolarizations. ..
  40. Chopra N, Yang T, Asghari P, Moore E, Huke S, Akin B, et al. Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A. 2009;106:7636-41 pubmed publisher
  41. Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener J, et al. Dominant role of smooth muscle L-type calcium channel Cav1.2 for blood pressure regulation. EMBO J. 2003;22:6027-34 pubmed
    ..2 channel. These results show that Cav1.2 calcium channels are key players in the hormonal regulation of blood pressure and development of myogenic tone. ..
  42. Driver J, Racca C, Cunningham M, Towers S, Davies C, Whittington M, et al. Impairment of hippocampal gamma-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP). Eur J Neurosci. 2007;26:1280-8 pubmed
    ..These data suggest that deficits in network function in Alzheimer's disease occur early and are not directly correlated to amyloid load. ..
  43. Blaich A, Pahlavan S, Tian Q, Oberhofer M, Poomvanicha M, Lenhardt P, et al. Mutation of the calmodulin binding motif IQ of the L-type Ca(v)1.2 Ca2+ channel to EQ induces dilated cardiomyopathy and death. J Biol Chem. 2012;287:22616-25 pubmed publisher
    ..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. ..
  44. Leiria L, Sollon C, Calixto M, Lintomen L, Mónica F, Anhê G, et al. Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice. PLoS ONE. 2012;7:e48507 pubmed publisher
    ..It is likely that insulin resistance importantly contributes for the pathophysiology of this urological disorder in obese mice. ..
  45. Terrillion C, Francis T, Puche A, Lobo M, Gould T. Decreased Nucleus Accumbens Expression of Psychiatric Disorder Risk Gene Cacna1c Promotes Susceptibility to Social Stress. Int J Neuropsychopharmacol. 2017;20:428-433 pubmed publisher
    Polymorphisms in the CACNA1C gene are associated with human mood disorders. The rodent social defeat model of stress/mood-disorder susceptibility results in maladaptive consequences mediated by altered function of mesolimbic circuits...
  46. Rosati B, Yan Q, Lee M, Liou S, Ingalls B, Foell J, et al. Robust L-type calcium current expression following heterozygous knockout of the Cav1.2 gene in adult mouse heart. J Physiol. 2011;589:3275-88 pubmed publisher
    ..The results are consistent with a model of L-type calcium channel biosynthesis in which there are one or more saturated steps, which act to buffer changes in both total Cav1.2 protein and L-type current expression. ..
  47. Völkening B, Schönig K, Kronenberg G, Bartsch D, Weber T. Deletion of psychiatric risk gene Cacna1c impairs hippocampal neurogenesis in cell-autonomous fashion. Glia. 2017;65:817-827 pubmed publisher
    ..b>CACNA1C, the gene encoding the alpha-1C subunit (i.e., Cav 1...
  48. Altier C, Dubel S, Barrere C, Jarvis S, Stotz S, Scott J, et al. AKAP79 modulation of L-type channels involves disruption of intramolecular interactions in the CaV1.2 subunit. Channels (Austin). 2012;6:157-65 pubmed publisher
    ..2. Thus, our results suggest that the effects of AKAP79 occur through relief of an autoinhibitory mechanism mediated by intramolecular interactions of Ca(v)1.2 intracellular regions. ..
  49. Huang G, Yao J, Zeng W, Mizuno Y, Kamm K, Stull J, et al. ER stress disrupts Ca2+-signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice. J Cell Sci. 2006;119:153-61 pubmed
  50. Koschak A, Obermair G, Pivotto F, Sinnegger Brauns M, Striessnig J, Pietrobon D. Molecular nature of anomalous L-type calcium channels in mouse cerebellar granule cells. J Neurosci. 2007;27:3855-63 pubmed
    ..2005), we discuss the hypothesis that anomalous rather than cardiac-type Ca(v)1.2 channels are specifically involved in LTCC-dependent and gene transcription-dependent LTP. ..
  51. Kryshtal D, Gryshchenko O, Gómez Hurtado N, Knollmann B. Impaired calcium-calmodulin-dependent inactivation of Cav1.2 contributes to loss of sarcoplasmic reticulum calcium release refractoriness in mice lacking calsequestrin 2. J Mol Cell Cardiol. 2015;82:75-83 pubmed publisher
    ..2, which contributes to the loss of SR Ca(2+) release refractoriness in the Casq2 KO mouse model and, therefore, may further increase risk for ventricular arrhythmia in vivo. ..
  52. Fu Y, Westenbroek R, Yu F, Clark J, Marshall M, Scheuer T, et al. Deletion of the distal C terminus of CaV1.2 channels leads to loss of beta-adrenergic regulation and heart failure in vivo. J Biol Chem. 2011;286:12617-26 pubmed publisher
    ..2 channels is required in vivo for normal vascular regulation, cell-surface expression of CaV1.2 channels in cardiac myocytes, and ?-adrenergic stimulation of L-type Ca2+ currents in the heart. ..
  53. Campbell D, Hess E. L-type calcium channels contribute to the tottering mouse dystonic episodes. Mol Pharmacol. 1999;55:23-31 pubmed
    ..The susceptibility of L-type calcium channels to voltage-dependent facilitation may promote this abnormal motor phenotype. ..
  54. Fassler R, Rohwedel J, Maltsev V, Bloch W, Lentini S, Guan K, et al. Differentiation and integrity of cardiac muscle cells are impaired in the absence of beta 1 integrin. J Cell Sci. 1996;109 ( Pt 13):2989-99 pubmed
    ..Thus, we conclude that interactions with the extracellular matrix via beta 1 integrin is necessary for differentiation and the maintenance of a specialized phenotype of cardiac muscle cells. ..
  55. Santiago González D, Cheli V, Zamora N, Lama T, Spreuer V, Murphy G, et al. Conditional Deletion of the L-Type Calcium Channel Cav1.2 in NG2-Positive Cells Impairs Remyelination in Mice. J Neurosci. 2017;37:10038-10051 pubmed publisher
    ..These findings could lead to novel approaches for obtaining a better understanding of the factors that control OPC maturation in order to stimulate this pool of progenitors to replace myelin in demyelinating diseases. ..
  56. Tang G, Zhang L, Yang G, Wu L, Wang R. Hydrogen sulfide-induced inhibition of L-type Ca2+ channels and insulin secretion in mouse pancreatic beta cells. Diabetologia. 2013;56:533-41 pubmed publisher
    ..Exogenous and endogenous H(2)S inhibit L-type VDCC activity and pancreatic insulin secretion, constituting a novel mechanism for the regulation of insulin secretion by the CSE/H(2)S system. ..
  57. Levin M, Singh G, Zhang H, Uchida K, Kozel B, Stein P, et al. K(ATP) channel gain-of-function leads to increased myocardial L-type Ca(2+) current and contractility in Cantu syndrome. Proc Natl Acad Sci U S A. 2016;113:6773-8 pubmed publisher
    ..2 at Ser1928, suggesting enhanced protein kinase activity as a potential link between increased KATP current and CS cardiac pathophysiology. ..
  58. Lin S, Tzeng B, Lee K, Smith R, Campbell K, Chen C. Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage. Proc Natl Acad Sci U S A. 2014;111:E1990-8 pubmed publisher
    ..Our findings define a previously unidentified mechanism that Ca(2+) influx via the Cav3.2 T-type Ca(2+) channel regulates Sox9 expression through the calcineurin/NFAT signaling pathway during tracheal chondrogenesis. ..
  59. Porter G, Makuck R, Rivkees S. Intracellular calcium plays an essential role in cardiac development. Dev Dyn. 2003;227:280-90 pubmed
    ..These data demonstrate that proper intracellular calcium signaling is essential for normal cardiac looping, gene expression, and organ development. ..
  60. Moosmang S, Haider N, Klugbauer N, Adelsberger H, Langwieser N, Müller J, et al. Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci. 2005;25:9883-92 pubmed
    ..and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1.2) gene in the hippocampus and neocortex (Cav1.2(HCKO))...
  61. Suzuki Y, Yoshimaru T, Inoue T, Ra C. Ca v 1.2 L-type Ca2+ channel protects mast cells against activation-induced cell death by preventing mitochondrial integrity disruption. Mol Immunol. 2009;46:2370-80 pubmed publisher
    ..These findings suggest that Ca(v)1.2 LTCC protects mast cells against activation-induced cell death by preventing mitochondrial integrity disruption. ..
  62. McKinney B, Sze W, White J, Murphy G. L-type voltage-gated calcium channels in conditioned fear: a genetic and pharmacological analysis. Learn Mem. 2008;15:326-34 pubmed publisher
    ..Taken together, our genetic and pharmacological data argue against a role for Ca(v)1.2 in consolidation of conditioned fear as well as a role for L-VGCCs in extinction of conditioned fear. ..
  63. Lee T, Karl R, Moosmang S, Lenhardt P, Klugbauer N, Hofmann F, et al. Calmodulin kinase II is involved in voltage-dependent facilitation of the L-type Cav1.2 calcium channel: Identification of the phosphorylation sites. J Biol Chem. 2006;281:25560-7 pubmed
    ..2 protein was strongly decreased in the S1512A/S1570A double mutant. These results suggest that voltage-dependent facilitation of the Ca(v)1.2 channel depends on the phosphorylation of Ser1512/Ser1570 by calmodulin kinase II. ..
  64. Zhang J, Berra Romani R, Sinnegger Brauns M, Striessnig J, Blaustein M, Matteson D. Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+. Am J Physiol Heart Circ Physiol. 2007;292:H415-25 pubmed
    ..The results indicate that Mg(2+) relaxes MT by inhibiting Ca(2+) influx through LVGCs. These data provide new information about the central role of Ca(v)1.2 LVGCs in generating and maintaining MT in mouse mesenteric small arteries. ..
  65. Lacinova L, Moosmang S, Langwieser N, Hofmann F, Kleppisch T. Cav1.2 calcium channels modulate the spiking pattern of hippocampal pyramidal cells. Life Sci. 2008;82:41-9 pubmed
    ..2 channels are involved in regulating the intrinsic excitability of CA1 pyramidal neurons. This cellular mechanism may contribute to the known function of Ca(v)1.2 channels in supporting synaptic plasticity and memory. ..
  66. Huster M, Frei E, Hofmann F, Wegener J. A complex of Ca(V)1.2/PKC is involved in muscarinic signaling in smooth muscle. FASEB J. 2010;24:2651-9 pubmed publisher
    ..2 is a substrate for PKC-mediated phosphorylation. These findings suggest that a signaling complex consisting of Ca(V)1.2, PKC, and, probably, PLD controls muscarinic-mediated phasic contraction of urinary bladder smooth muscle...
  67. Enes J, Langwieser N, Ruschel J, Carballosa Gonzalez M, Klug A, Traut M, et al. Electrical activity suppresses axon growth through Ca(v)1.2 channels in adult primary sensory neurons. Curr Biol. 2010;20:1154-64 pubmed publisher
    ..Our data indicate that cessation of electrical activity after peripheral lesion contributes to the regenerative response observed upon conditioning and might be necessary to promote regeneration after central nervous system injury. ..
  68. Heineke J, Auger Messier M, Correll R, Xu J, Benard M, Yuan W, et al. CIB1 is a regulator of pathological cardiac hypertrophy. Nat Med. 2010;16:872-9 pubmed publisher
    ..Thus, CIB1 functions as a previously undescribed regulator of cardiac hypertrophy through its ability to regulate the association of calcineurin with the sarcolemma and its activation. ..
  69. Hartman M, Liu Y, Zhu W, Chien W, Weldy C, Fishman G, et al. Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte action potential and mild conduction system expansion but does not alter conduction system function or promote spontaneous arrhythmias. FASEB J. 2014;28:3007-15 pubmed publisher
    ..CHF1/Hey2-KO mice demonstrate a 50% reduction in action potential dV/dT, a 50-75% reduction in SCN5A, KCNJ2, and CACNA1C ion channel subunit gene expression, and an increase in delayed afterdepolarizations from 0/min to 12/min...
  70. Fernández Tenorio M, Porras González C, Castellano A, del Valle Rodriguez A, Lopez Barneo J, Ureña J. Metabotropic regulation of RhoA/Rho-associated kinase by L-type Ca2+ channels: new mechanism for depolarization-evoked mammalian arterial contraction. Circ Res. 2011;108:1348-57 pubmed publisher
  71. Emrick M, Sadilek M, Konoki K, Catterall W. Beta-adrenergic-regulated phosphorylation of the skeletal muscle Ca(V)1.1 channel in the fight-or-flight response. Proc Natl Acad Sci U S A. 2010;107:18712-7 pubmed publisher
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    ..The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction...
  73. Waka N, Knipper M, Engel J. Localization of the calcium channel subunits Cav1.2 (alpha1C) and Cav2.3 (alpha1E) in the mouse organ of Corti. Histol Histopathol. 2003;18:1115-23 pubmed publisher
    ..Around P14, Cav2.3 immunoreactivity disappeared from these structures and from P19 onwards it was observed in the basal poles of the outer hair cell membranes. ..
  74. Leitch B, Shevtsova O, Guevremont D, Williams J. Loss of calcium channels in the cerebellum of the ataxic and epileptic stargazer mutant mouse. Brain Res. 2009;1279:156-67 pubmed publisher
    ..It is therefore possible that stargazin is involved in the trafficking of both AMPARs and VDCCs or in the formation of a functional AMPA receptor-calcium channel complex in the postsynaptic membrane. ..
  75. Schroder E, Byse M, Satin J. L-type calcium channel C terminus autoregulates transcription. Circ Res. 2009;104:1373-81 pubmed publisher
    ..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. ..
  76. Lester W, Schroder E, Burgess D, Yozwiak D, Andres D, Satin J. Steady-state coupling of plasma membrane calcium entry to extrusion revealed by novel L-type calcium channel block. Cell Calcium. 2008;44:353-62 pubmed
    ..We conclude that chronic block of Ca(v)1.2 channel-mediated SL entry alters NCX expression, and coincidentally controls SR Ca loading and SL Ca2+ efflux. ..
  77. Zhang X, Wang J, Song J, Rabinowitz J, Chen X, Houser S, et al. Regulation of L-type calcium channel by phospholemman in cardiac myocytes. J Mol Cell Cardiol. 2015;84:104-11 pubmed publisher
    ..We conclude that PLM limits Ca(2+) influx in cardiac myocytes by reducing maximal ICa and accelerating voltage-dependent inactivation. ..
  78. Helton T, Xu W, Lipscombe D. Neuronal L-type calcium channels open quickly and are inhibited slowly. J Neurosci. 2005;25:10247-51 pubmed
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    ..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. ..
  80. Wang F, Du T, Liang C, Verkhratsky A, Peng L. Ammonium increases Ca(2+) signalling and upregulates expression of Cav1.2 gene in astrocytes in primary cultures and in the in vivo brain. Acta Physiol (Oxf). 2015;214:261-74 pubmed publisher
    ..2 mRNA expression was upregulated in astrocytes, but not in neurones. Ammonium-induced deregulation of astroglial Ca(2+) signalling, is, in part, associated with upregulation of Cav1.2 L-type calcium channels. ..
  81. Furtado M, Wilmanns J, Chandran A, Tonta M, Biben C, Eichenlaub M, et al. A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels. Differentiation. 2016;91:29-41 pubmed publisher
  82. Navedo M, Amberg G, Westenbroek R, Sinnegger Brauns M, Catterall W, Striessnig J, et al. Ca(v)1.3 channels produce persistent calcium sparklets, but Ca(v)1.2 channels are responsible for sparklets in mouse arterial smooth muscle. Am J Physiol Heart Circ Physiol. 2007;293:H1359-70 pubmed
    ..We conclude that although Ca(v)1.3 channels can produce Ca(2+) sparklets, Ca(v)1.2 channels underlie I(Ca), Ca(2+) sparklets, and hence dihydropyridine-sensitive Ca(2+) influx in mouse arterial myocytes. ..
  83. Pan J, Yuan S, Yu T, Su C, Liu X, He J, et al. Regulation of L-type Ca2+ Channel Activity and Insulin Secretion by Huntingtin-associated Protein 1. J Biol Chem. 2016;291:26352-26363 pubmed
    ..2, providing new insight into the mechanisms that regulate insulin release from pancreatic ?-cells. ..
  84. Sun Z, Cao X, Zhang Z, Hu Z, Zhang L, Wang H, et al. Simulated microgravity inhibits L-type calcium channel currents partially by the up-regulation of miR-103 in MC3T3-E1 osteoblasts. Sci Rep. 2015;5:8077 pubmed publisher
    ..Our study provides a novel mechanism for microgravity-induced detrimental effects on osteoblasts, offering a new avenue to further investigate the bone loss induced by microgravity. ..
  85. Di Biase V, Obermair G, Szabo Z, Altier C, Sanguesa J, Bourinet E, et al. Stable membrane expression of postsynaptic CaV1.2 calcium channel clusters is independent of interactions with AKAP79/150 and PDZ proteins. J Neurosci. 2008;28:13845-55 pubmed publisher
    ..2 is independent of its interactions with AKAP79/150 and PDZ proteins. ..
  86. Mahapatra S, Marcantoni A, Zuccotti A, Carabelli V, Carbone E. Equal sensitivity of Cav1.2 and Cav1.3 channels to the opposing modulations of PKA and PKG in mouse chromaffin cells. J Physiol. 2012;590:5053-73 pubmed publisher
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    ..2 expression. These findings indicate that absence of the carboxyl-terminal tail differentially determines the fate of the cardiac and smooth muscle splice variant of the CaV1.2 channel in the mouse. ..
  89. Etemad S, Obermair G, Bindreither D, Benedetti A, Stanika R, Di Biase V, et al. Differential neuronal targeting of a new and two known calcium channel ?4 subunit splice variants correlates with their regulation of gene expression. J Neurosci. 2014;34:1446-61 pubmed publisher
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