Genomes and Genes
Gene Symbol: Cacna1b
Description: calcium channel, voltage-dependent, N type, alpha 1B subunit
Alias: AW050276, AW060892, AW822256, BIII, Cav2.2, Cchn1a, alpha(1B), voltage-dependent N-type calcium channel subunit alpha-1B, brain calcium channel III, calcium channel, L type, alpha-1 polypeptide, calcium channel, voltage-dependent, L type, alpha 1B subunit, calcium channel, voltage-dependent, N type, alpha 1B subunit, BIII, voltage-gated calcium channel subunit alpha Cav2.2
- Newton P, Orr C, Wallace M, Kim C, Shin H, Messing R. Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice. J Neurosci. 2004;24:9862-9 pubmed..These results demonstrate that N-type calcium channels modulate acute responses to ethanol and are important mediators of ethanol reward and preference. ..
- Murakami M, Ohba T, Takahashi Y, Watanabe H, Miyoshi I, Nakayama S, et al. Identification of a cardiac isoform of the murine calcium channel alpha1C (Cav1.2-a) subunit and its preferential binding with the beta2 subunit. J Mol Cell Cardiol. 2006;41:115-25 pubmed..In vitro overlay and immunoprecipitation analyses revealed preferential binding between alpha1C-a and beta2, which is also expressed at a high level in the heart. ..
- Kim C, Jun K, Lee T, Kim S, McEnery M, Chin H, et al. Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel. Mol Cell Neurosci. 2001;18:235-45 pubmed..These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level. ..
- Ricoy U, FRERKING M. Distinct roles for Cav2.1-2.3 in activity-dependent synaptic dynamics. J Neurophysiol. 2014;111:2404-13 pubmed publisher..Thus different Cav2 channels vary in their coupling to synaptic transmission over different frequency ranges, with consequences for the frequency tuning of both synaptic dynamics and presynaptic neuromodulation. ..
- Motagally M, Neshat S, Lomax A. Inhibition of sympathetic N-type voltage-gated Ca2+ current underlies the reduction in norepinephrine release during colitis. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1077-84 pubmed publisher..This may contribute to functional alterations in both inflamed and uninflamed regions of the GI tract during inflammation. ..
- Brittain J, Piekarz A, Wang Y, Kondo T, Cummins T, Khanna R. An atypical role for collapsin response mediator protein 2 (CRMP-2) in neurotransmitter release via interaction with presynaptic voltage-gated calcium channels. J Biol Chem. 2009;284:31375-90 pubmed publisher..Toxin block of Ca(2+) entry via CaV2.2 abolished this stimulated release. Thus, the CRMP-2-Ca(2+) channel interaction represents a novel mechanism for modulation of Ca(2+) influx into nerve terminals and, hence, of synaptic strength. ..
- Templin J, Bang S, Soiza Reilly M, Berde C, Commons K. Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas. Brain Res. 2012;1457:1-12 pubmed publisher..The identified genes likely contribute to unique excitable properties of different groups of neurons in the DR and may include novel pharmacologic targets for affective disorders. ..
- Koch H, Zanella S, Elsen G, Smith L, Doi A, Garcia A, et al. Stable respiratory activity requires both P/Q-type and N-type voltage-gated calcium channels. J Neurosci. 2013;33:3633-45 pubmed publisher..In the absence of P/Q-type calcium channels, breathing, sighing, and neuromodulation are severely compromised, leading to early mortality. ..
- Takahashi E, Nagasu T. Pattern of compensatory expression of voltage-dependent Ca2+ channel alpha1 and beta subunits in brain of N-type Ca2+ channel alpha1B subunit gene-deficient mice with a CBA/JN genetic background. Exp Anim. 2005;54:29-36 pubmed..These results suggest that the compensatory mechanisms differ in different brain regions of alpha(1B)-deficient mice with a CBA/JN genetic background. ..
- Coppola T, Waldmann R, Borsotto M, Heurteaux C, Romey G, Mattei M, et al. Molecular cloning of a murine N-type calcium channel alpha 1 subunit. Evidence for isoforms, brain distribution, and chromosomal localization. FEBS Lett. 1994;338:1-5 pubmed..The N-type Ca2+ channel gene has been localized on the chromosome 2, band A. ..
- Waterman S. Multiple subtypes of voltage-gated calcium channel mediate transmitter release from parasympathetic neurons in the mouse bladder. J Neurosci. 1996;16:4155-61 pubmed..Furthermore, the release of the two main transmitters in these neurons has differing dependencies on the calcium channel subtypes. ..
- Mynlieff M, Beam K. Adenosine acting at an A1 receptor decreases N-type calcium current in mouse motoneurons. J Neurosci. 1994;14:3628-34 pubmed..Thus, it is uncertain what motoneuronal functions are influenced by adenosine modulation of N-type channels. ..
- 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. ..
- Hatakeyama S, Wakamori M, Ino M, Miyamoto N, Takahashi E, Yoshinaga T, et al. Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca(2+) channels. Neuroreport. 2001;12:2423-7 pubmed..These results suggest a crucial role of N-type channels in nociceptive transmission, especially for persistent pain like phase 2 of the formalin test and for nociception induced by thermal stimuli. ..
- Murakami M, Ohba T, Wu T, Fujisawa S, Suzuki T, Takahashi Y, et al. Modified sympathetic regulation in N-type calcium channel null-mouse. Biochem Biophys Res Commun. 2007;354:1016-20 pubmed..Combined, our biochemical and physiological analyses strongly suggest that the remaining sympathetic tonus in NKO mice is dependent on R-type calcium channels. ..
- Cahill A, Hurley J, Fox A. Coexpression of cloned alpha(1B), beta(2a), and alpha(2)/delta subunits produces non-inactivating calcium currents similar to those found in bovine chromaffin cells. J Neurosci. 2000;20:1685-93 pubmed
- Jeon D, Kim C, Yang Y, Rhim H, Yim E, Oh U, et al. Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice. Genes Brain Behav. 2007;6:375-88 pubmed..Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP. ..
- Girard L, Hanna Z, Beaulieu N, Hoemann C, Simard C, Kozak C, et al. Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Genes Dev. 1996;10:1930-44 pubmed..Furthermore, our data indicate that Notch1 alleles mutated by provirus insertion can lead to increased expression of truncated and full-length (330/280-kD) Notch1 proteins, both being produced in a cleaved and uncleaved form. ..
- Chen J, Billings S, Nishimune H. Calcium channels link the muscle-derived synapse organizer laminin ?2 to Bassoon and CAST/Erc2 to organize presynaptic active zones. J Neurosci. 2011;31:512-25 pubmed publisher..These results suggest that presynaptic VDCCs link the target-derived synapse organizer laminin ?2 to active-zone proteins and function as scaffolding proteins to anchor active-zone proteins to the presynaptic membrane. ..
- Trimarchi J, Stadler M, Roska B, Billings N, Sun B, Bartch B, et al. Molecular heterogeneity of developing retinal ganglion and amacrine cells revealed through single cell gene expression profiling. J Comp Neurol. 2007;502:1047-65 pubmed..In addition, this study has allowed for the definition of some of the molecular heterogeneity both between developing ganglion and amacrine cells and among subclasses of each cell type. ..
- Ino M, Yoshinaga T, Wakamori M, Miyamoto N, Takahashi E, Sonoda J, et al. Functional disorders of the sympathetic nervous system in mice lacking the alpha 1B subunit (Cav 2.2) of N-type calcium channels. Proc Natl Acad Sci U S A. 2001;98:5323-8 pubmed
- Takahashi E, Ito M, Miyamoto N, Nagasu T, Ino M, Tanaka I. Increased glucose tolerance in N-type Ca2+ channel alpha(1B)-subunit gene-deficient mice. Int J Mol Med. 2005;15:937-44 pubmed..Thus, N-type Ca2+ channel blockers might be candidate anti-diabetic/anti-obesity agents. ..
- Beuckmann C, Sinton C, Miyamoto N, Ino M, Yanagisawa M. N-type calcium channel alpha1B subunit (Cav2.2) knock-out mice display hyperactivity and vigilance state differences. J Neurosci. 2003;23:6793-7 pubmed..2-/- mice. These results indicate a role of the N-type Ca2+ channel in activity and vigilance state control, which we interpret in terms of effects on neurotransmitter release. ..
- Duan J, Hodgdon K, Hingtgen C, Nicol G. N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1+/- mice. Neuroscience. 2014;270:192-202 pubmed publisher..Thus, our results demonstrate that sensory neurons from Nf1+/- mice, exhibit increased N-type ICa and likely account for the increased release of substance P and calcitonin gene-related peptide that occurs in Nf1+/- sensory neurons. ..
- Allen S, Toro C, Andrade A, Lopez Soto E, Denome S, Lipscombe D. Cell-Specific RNA Binding Protein Rbfox2 Regulates CaV2.2 mRNA Exon Composition and CaV2.2 Current Size. Eneuro. 2017;4: pubmed publisher..Many ion channel genes undergo extensive alternative splicing including Cacna1b that encodes the voltage-gated CaV2.2 ?1 subunit...
- Ladera C, Martín R, Bartolomé Martín D, Torres M, Sánchez Prieto J. Partial compensation for N-type Ca(2+) channel loss by P/Q-type Ca(2+) channels underlines the differential release properties supported by these channels at cerebrocortical nerve terminals. Eur J Neurosci. 2009;29:1131-40 pubmed publisher..We conclude that the glutamate release supported by N- and P/Q-type channels exhibits distinct properties, and that P/Q-type channels cannot fully compensate for the loss of N-type channels. ..
- Huynh T, Cuny H, Slesinger P, Adams D. Novel mechanism of voltage-gated N-type (Cav2.2) calcium channel inhibition revealed through Î±-conotoxin Vc1.1 activation of the GABA(B) receptor. Mol Pharmacol. 2015;87:240-50 pubmed publisher..2 channels. These findings provide important insights into how GABA(B)Rs mediate Cav2.2 channel inhibition and alter nociceptive transmission. ..
- Baddack U, Frahm S, Antolin Fontes B, Grobe J, Lipp M, MÃ¼ller G, et al. Suppression of Peripheral Pain by Blockade of Voltage-Gated Calcium 2.2 Channels in Nociceptors Induces RANKL and Impairs Recovery From Inflammatory Arthritis in a Mouse Model. Arthritis Rheumatol. 2015;67:1657-67 pubmed publisher..2- mediated calcium influx and signaling in nociceptor sensory neurons impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV 2.2 channel blockers as analgesics during inflammation. ..
- Weiss J, Pyrski M, Weissgerber P, Zufall F. Altered synaptic transmission at olfactory and vomeronasal nerve terminals in mice lacking N-type calcium channel Cav2.2. Eur J Neurosci. 2014;40:3422-35 pubmed publisher..In Cacna1b mutant mice lacking the Cav2...
- Newton P, Zeng L, Wang V, Connolly J, Wallace M, Kim C, et al. A blocker of N- and T-type voltage-gated calcium channels attenuates ethanol-induced intoxication, place preference, self-administration, and reinstatement. J Neurosci. 2008;28:11712-9 pubmed publisher..These results suggest that selective calcium channel inhibitors may be useful in reducing acute ethanol intoxication and alcohol consumption by human alcoholics. ..
- Murakami M, Ohba T, Xu F, Satoh E, Miyoshi I, Suzuki T, et al. Modified sympathetic nerve system activity with overexpression of the voltage-dependent calcium channel beta3 subunit. J Biol Chem. 2008;283:24554-60 pubmed publisher..These results identify a determining role for the beta3 subunit in the N-type channel population in SCG and a major role in sympathetic nerve regulation. ..
- Samuels B, Hsueh Y, Shu T, Liang H, Tseng H, Hong C, et al. Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron. 2007;56:823-37 pubmed..Functional consequences include alterations in calcium influx. Mechanistically, Cdk5 regulates the interaction between CASK and liprin-alpha. These results provide a molecular explanation of how Cdk5 can promote synaptogenesis. ..
- Szabo Z, Obermair G, Cooper C, Zamponi G, Flucher B. Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons. Eur J Neurosci. 2006;24:709-18 pubmed..The unique targeting properties of the splice variants lacking the synprint site are suggestive of specific functions of these calcium channels apart from activating fast synaptic transmission. ..
- Burgess D, Biddlecome G, McDonough S, Diaz M, Zilinski C, Bean B, et al. beta subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain. Mol Cell Neurosci. 1999;13:293-311 pubmed..The existence of beta subunit reshuffling demonstrates that molecular plasticity of Ca2+ channel assembly, a normal feature of early brain development, is retained in the mature brain. ..
- Takahashi E, Ino M, Miyamoto N, Nagasu T. Expression analysis of P/Q-type Ca2+ channel alpha 1A subunit mRNA in olfactory mitral cell in N-type Ca2+ channel alpha 1B subunit gene-deficient mice. Neurosci Lett. 2004;359:37-40 pubmed..5-kb 5'-upstream region of this gene contains an enhancer cis-element for compensation in olfactory mitral cells. ..
- Yamada Y, Kinoshita H, Kuwahara K, Nakagawa Y, Kuwabara Y, Minami T, et al. Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure. Cardiovasc Res. 2014;104:183-93 pubmed publisher..Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the ?1 subunit of NCCs, improved the survival rate...
- Saegusa H, Tanabe T. N-type voltage-dependent Ca2+ channel in non-excitable microglial cells in mice is involved in the pathophysiology of neuropathic pain. Biochem Biophys Res Commun. 2014;450:142-7 pubmed publisher..Although the mechanism of its activation is not clear at present, activation of N-type VDCC expressed in non-excitable microglial cells contributes to the pathophysiology of neuropathic pain. ..
- 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. ..
- Su S, Seo J, Pan J, Samuels B, Rudenko A, Ericsson M, et al. Regulation of N-type voltage-gated calcium channels and presynaptic function by cyclin-dependent kinase 5. Neuron. 2012;75:675-87 pubmed publisher..Collectively, our results highlight a molecular mechanism by which N-type calcium channels are regulated by Cdk5 to affect presynaptic function. ..
- Marangoudakis S, Andrade A, Helton T, Denome S, Castiglioni A, Lipscombe D. Differential ubiquitination and proteasome regulation of Ca(V)2.2 N-type channel splice isoforms. J Neurosci. 2012;32:10365-9 pubmed publisher..2 encoded by exon 37b of the mouse Cacna1b gene predispose cloned and native channels to downregulation by the UPS. Ca(V)2...
- Mallmann R, Wilmes T, Lichvárová L, Bührer A, Lohmüller B, Castonguay J, et al. Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels. Sci Rep. 2013;3:1777 pubmed publisher..2. These data indicate that TSPAN-13 might regulate CaV2.2 Ca(2+) channel activity in defined synaptic membrane compartments and thereby influences transmitter release. ..
- Takei T, Saegusa H, Zong S, Murakoshi T, Makita K, Tanabe T. Increased sensitivity to halothane but decreased sensitivity to propofol in mice lacking the N-type Ca2+ channel. Neurosci Lett. 2003;350:41-5 pubmed..In contrast, sensitivity to propofol was significantly decreased in the knockout mice. We suggest that inhibition of the N-type Ca2+ channel underlies mechanisms of halothane anesthesia but counteracts propofol anesthesia. ..
- Barsukova A, Forte M, Bourdette D. Focal increases of axoplasmic Ca2+, aggregation of sodium-calcium exchanger, N-type Ca2+ channel, and actin define the sites of spheroids in axons undergoing oxidative stress. J Neurosci. 2012;32:12028-37 pubmed publisher..This study provides new insights into the mechanism of a spheroid formation at specific sites along axons undergoing oxidative stress and a basis for new neuroprotective strategies. ..
- 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. ..
- Kline C, Scott J, Curran J, Hund T, Mohler P. Ankyrin-B regulates Cav2.1 and Cav2.2 channel expression and targeting. J Biol Chem. 2014;289:5285-95 pubmed publisher..Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo. ..
- Murakami M, Nakagawasai O, Suzuki T, Mobarakeh I, Sakurada Y, Murata A, et al. Antinociceptive effect of different types of calcium channel inhibitors and the distribution of various calcium channel alpha 1 subunits in the dorsal horn of spinal cord in mice. Brain Res. 2004;1024:122-9 pubmed..The results of this study revealed the localization and functions of several calcium channels that are involved in nociceptive neurotransmission within the dorsal horn of the mouse spinal cord. ..
- Takahashi E, Nagasu T. Enhanced expression of Ca2+ channel alpha1A and beta4 subunits and phosphorylated tyrosine hydroxylase in the adrenal gland of N-type Ca2+ channel alpha1B subunit-deficient mice with a CBA/JN genetic background. Comp Med. 2006;56:168-75 pubmed
- Gandini M, Henríquez D, Grimaldo L, Sandoval A, Altier C, Zamponi G, et al. CaV2.2 channel cell surface expression is regulated by the light chain 1 (LC1) of the microtubule-associated protein B (MAP1B) via UBE2L3-mediated ubiquitination and degradation. Pflugers Arch. 2014;466:2113-26 pubmed publisher..Together these results revealed a novel functional coupling between LC1 and the N-type channels. ..
- Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer R, Gottmann K, et al. Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature. 2003;423:939-48 pubmed..These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery. ..
- Fischer M, Pereira P, Holtmann B, Simon C, Hanauer A, Heisenberg M, et al. P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons. Mol Cell Neurosci. 2009;42:134-41 pubmed publisher..Thus, the functional defects observed in the nervous system of CLS patients and animal models with Rsk2 deficiency might be caused by dysregulated neurite growth rather than primary neurodegeneration. ..
- Takahashi E, Ino M, Miyamoto N, Nagasu T. Increased expression of P/Q-type Ca2+ channel alpha1A subunit mRNA in cerebellum of N-type Ca2+ channel alpha1B subunit gene-deficient mice. Brain Res Mol Brain Res. 2004;124:79-87 pubmed..0-kb 5'-upstream region of alpha(1A) subunit gene contains an enhancer cis-element(s) for compensation in cerebellar granule cells. ..
- Yamazaki K, Shigetomi E, Ikeda R, Nishida M, Kiyonaka S, Mori Y, et al. Blocker-resistant presynaptic voltage-dependent Ca2+ channels underlying glutamate release in mice nucleus tractus solitarii. Brain Res. 2006;1104:103-13 pubmed
- Yokoyama K, Kurihara T, Saegusa H, Zong S, Makita K, Tanabe T. Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine tolerance. Eur J Neurosci. 2004;20:3516-9 pubmed..3(-/-) mice. Furthermore, i.c.v. administration of an R-type channel blocker potentiated morphine analgesia in wild-type mice. Thus, the inhibition of R-type Ca(2+) current could lead to high-efficiency opioid therapy without tolerance. ..
- Wang D, Fisher T. Expression of CaV 2.2 and splice variants of CaV 2.1 in oxytocin- and vasopressin-releasing supraoptic neurones. J Neuroendocrinol. 2014;26:100-10 pubmed publisher..1 in VP and OT MNCs, as well as the expression in MNCs of deletion variants of Ca(V)2.1 that do not interact with exocytotic proteins and therefore may be less likely to mediate exocytotic release. ..
- Nishida M, Ishikawa T, Saiki S, Sunggip C, Aritomi S, Harada E, et al. Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice. Biochem Biophys Res Commun. 2013;434:210-6 pubmed publisher..These results suggest that N-type VDCCs expressed in the vascular endothelial cells contribute to ROS production and endothelial dysfunction observed in Ang II-treated hypertensive mice. ..
- Murakami M, Matsui H, Shiraiwa T, Suzuki T, Sasano H, Takahashi E, et al. Decreases in pheromonal responses at the accessory olfactory bulb of mice with a deficiency of the alpha1B or beta3 subunits of voltage-dependent Ca2+-channels. Biol Pharm Bull. 2006;29:437-42 pubmed..These data suggest the importance of the alpha1B and beta3 subunits of the N-type voltage-dependent Ca2+ channel for the pheromone signal transduction system. ..
- Chan A, Khanna R, Li Q, Stanley E. Munc18: a presynaptic transmitter release site N type (CaV2.2) calcium channel interacting protein. Channels (Austin). 2007;1:11-20 pubmed..Thus, the calcium channel may serve as a surface membrane platform anchoring a Munc18-containing bridge to synaptotagmin and the synaptic vesicle. ..