Genomes and Genes
q type calcium channels
Summary: CALCIUM CHANNELS located in the neurons of the brain.
- Fletcher C, Tottene A, Lennon V, Wilson S, Dubel S, Paylor R, et al. Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. FASEB J. 2001;15:1288-90 pubmed
- Doyle J, Ren X, Lennon G, Stubbs L. Mutations in the Cacnl1a4 calcium channel gene are associated with seizures, cerebellar degeneration, and ataxia in tottering and leaner mutant mice. Mamm Genome. 1997;8:113-20 pubmed
- Fletcher C, Lutz C, O Sullivan T, Shaughnessy J, Hawkes R, Frankel W, et al. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell. 1996;87:607-17 pubmed..These studies define the first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel and identify the first gene involved in absence epilepsy. ..
- Jun K, Piedras Rentería E, Smith S, Wheeler D, Lee S, Lee T, et al. Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit. Proc Natl Acad Sci U S A. 1999;96:15245-50 pubmed..The alpha(1A)(-/-) mice provide a starting point for unraveling neuropathological mechanisms of human diseases generated by mutations in alpha(1A). ..
- Plomp J, Vergouwe M, van den Maagdenberg A, Ferrari M, Frants R, Molenaar P. Abnormal transmitter release at neuromuscular junctions of mice carrying the tottering alpha(1A) Ca(2+) channel mutation. Brain. 2000;123 Pt 3:463-71 pubmed..This study shows that functional consequences of alpha(1A) mutations causing cerebral disorders can be characterized at the NMJ. ..
- Zwingman T, Neumann P, Noebels J, Herrup K. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci. 2001;21:1169-78 pubmed..Overall these findings point to an important dissociation between the seizure phenotypes and the abnormalities in catecholamine metabolism, and they emphasize the value of allelic series in the study of gene function. ..
- Stahl J, James R, Oommen B, Hoebeek F, De Zeeuw C. Eye movements of the murine P/Q calcium channel mutant tottering, and the impact of aging. J Neurophysiol. 2006;95:1588-607 pubmed..The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains. ..
- Wakamori M, Yamazaki K, Matsunodaira H, Teramoto T, Tanaka I, Niidome T, et al. Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel. J Biol Chem. 1998;273:34857-67 pubmed
- Matsushita K, Wakamori M, Rhyu I, Arii T, Oda S, Mori Y, et al. Bidirectional alterations in cerebellar synaptic transmission of tottering and rolling Ca2+ channel mutant mice. J Neurosci. 2002;22:4388-98 pubmed
- Knight Y, Bartsch T, Kaube H, Goadsby P. P/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine?. J Neurosci. 2002;22:RC213 pubmed..0001). These results demonstrate that P/Q-type calcium channels in the PAG play a role in modulating trigeminal nociception and suggest a role for dysfunctional P/Q-type calcium channels in migraine pathophysiology. ..
- Hsieh Y, Yang E, Hsu E, Chow Y, Kou R. Voltage-dependent calcium channels in the corpora allata of the adult male loreyi leafworm, Mythimna loreyi. Insect Biochem Mol Biol. 2002;32:547-57 pubmed..loreyi, and that the N-type VDCCs may play important roles in these cellular events. ..
- Piedras Rentería E, Watase K, Harata N, Zhuchenko O, Zoghbi H, Lee C, et al. Increased expression of alpha 1A Ca2+ channel currents arising from expanded trinucleotide repeats in spinocerebellar ataxia type 6. J Neurosci. 2001;21:9185-93 pubmed..Our results showed that Ca(2+) channels from SCA6 patients display near-normal biophysical properties but increased current density attributable to elevated protein expression at the cell surface. ..
- Dooley D, Donovan C, Meder W, Whetzel S. Preferential action of gabapentin and pregabalin at P/Q-type voltage-sensitive calcium channels: inhibition of K+-evoked [3H]-norepinephrine release from rat neocortical slices. Synapse. 2002;45:171-90 pubmed..These findings suggest a selective modulation of P/Q-type VSCC that are implicated in neurotransmission and several GBP-responsive pathologies. ..
- Kaja S, van de Ven R, Ferrari M, Frants R, van den Maagdenberg A, Plomp J. Compensatory contribution of Cav2.3 channels to acetylcholine release at the neuromuscular junction of tottering mice. J Neurophysiol. 2006;95:2698-704 pubmed..This is the first report of compensatory expression of non-Cav2.1 channels at NMJs of mice with a single amino acid change in Cav2.1. ..
- Millán C, Lujan R, Shigemoto R, Sánchez Prieto J. Subtype-specific expression of group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals. J Biol Chem. 2002;277:47796-803 pubmed..This specific coexpression of different group III mGluRs and Ca(2+) channels may endow synaptic terminals with distinct release properties and reveals the existence of a high degree of presynaptic heterogeneity. ..
- Takahashil E, Nagasu T. Genetic background influences P/Q-type Ca2+ channel alpha1A subunit mRNA expression in olfactory bulb and reproductive ability of N-type Ca2+ channel alpha1B subunit-deficient mice. Biochem Genet. 2005;43:287-98 pubmed..These results suggest that the genetic background influences alpha1A subunit mRNA expression and reproductive ability in alpha1B-deficient mice. ..
- Khavandgar S, Walter J, Sageser K, Khodakhah K. Kv1 channels selectively prevent dendritic hyperexcitability in rat Purkinje cells. J Physiol. 2005;569:545-57 pubmed..Further, we show that Kv1 channels also contribute to dendritic integration of parallel fibre synaptic input. Kv1 channels are often targeted to soma and axon and the data presented support a major dendritic function for these channels. ..
- Lee J, Yoon S, Bae I. Studies on Ca2+-channel distribution in maturation arrested mouse oocyte. Mol Reprod Dev. 2004;69:174-85 pubmed..In addition, we found evidence that a functional voltage-dependent Ca2+-channel (L-type) exists in mouse oocytes (ovulated and cultured MII staged oocytes by a confocal laser scanning microscope). ..
- Minami K, Raymond C, Martin Moutot N, Ohtake A, Van Renterghem C, Takahashi M, et al. Role of Thr(11) in the binding of omega-conotoxin MVIIC to N-type Ca2+ channels. FEBS Lett. 2001;491:127-30 pubmed..Inhibition of Ba2+ current by the analogs did not completely correlate with binding affinity, although binding to BHK cells was comparable to rat cerebellar membranes. ..
- Urbano F, Piedras Rentería E, Jun K, Shin H, Uchitel O, Tsien R. Altered properties of quantal neurotransmitter release at endplates of mice lacking P/Q-type Ca2+ channels. Proc Natl Acad Sci U S A. 2003;100:3491-6 pubmed..Changes in presynaptic function were also associated with a significant reduction in the size of postsynaptic acetylcholine receptor clusters. ..
- Johnson R, Gamblin R, Ooi L, Bruce A, Donaldson I, Westhead D, et al. Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication. Nucleic Acids Res. 2006;34:3862-77 pubmed..Most of these sequences are associated with transposable elements, leading us to propose that transposon-mediated duplication and insertion of RE1s has led to the acquisition of novel target genes by REST during evolution. ..
- Schleithoff L, Mehrke G, Reutlinger B, Lehmann Horn F. Genomic structure and functional expression of a human alpha(2)/delta calcium channel subunit gene (CACNA2). Genomics. 1999;61:201-9 pubmed..The sequence analysis provides the basis for comprehensive mutation screening of CACNA2 for putative MHS3 individuals and patients with other channelopathies. ..
- Sato K, Raymond C, Martin Moutot N, Sasaki T, Ohtake A, Minami K, et al. Binding of six chimeric analogs of omega-conotoxin MVIIA and MVIIC to N- and P/Q-type calcium channels. Biochem Biophys Res Commun. 2000;269:254-6 pubmed..The roles of these two residues were confirmed by synthesizing two MVIIC analogs in which Pro(7) and Thr(11) were replaced with Lys(7) and Leu(11), respectively. ..
- Millán C, Sánchez Prieto J. Differential coupling of N- and P/Q-type calcium channels to glutamate exocytosis in the rat cerebral cortex. Neurosci Lett. 2002;330:29-32 pubmed
- Kors E, van den Maagdenberg A, Plomp J, Frants R, Ferrari M. Calcium channel mutations and migraine. Curr Opin Neurol. 2002;15:311-6 pubmed..Transfection studies and mouse model analyses are currently being undertaken to study the correlation between CACNA1A mutations and disease. ..
- Ovsepian S, Friel D. The leaner P/Q-type calcium channel mutation renders cerebellar Purkinje neurons hyper-excitable and eliminates Ca2+-Na+ spike bursts. Eur J Neurosci. 2008;27:93-103 pubmed..Our data indicate that a deficit in P-type Ca2+ current leads to complex functional and structural changes in PCs, impairing their intrinsic and integrative properties. ..
- Adams P, Snutch T. Calcium channelopathies: voltage-gated calcium channels. Subcell Biochem. 2007;45:215-51 pubmed..At least in those instances wherein the channelopathies can be attributed to gain-of-function mechanisms, the data point towards new therapeutic strategies for developing highly selective calcium channel antagonists...
- Molenaar P. A relative weak leg muscle in the rolling Nagoya mouse as a model for Lambert-Eaton myasthenic syndrome. J Neuroimmunol. 2008;201-202:166-71 pubmed publisher..The results suggest that leg weakness in LEMS may result from a relatively small safety factor of neuromuscular transmission and that this could become particularly prominent when the activity of calcium channels is diminished. ..
- Martín R, Torres M, Sánchez Prieto J. mGluR7 inhibits glutamate release through a PKC-independent decrease in the activity of P/Q-type Ca2+ channels and by diminishing cAMP in hippocampal nerve terminals. Eur J Neurosci. 2007;26:312-22 pubmed..Thus, mGluR7 mediates the inhibition of glutamate release at hippocampal nerve terminals primarily by inhibiting P/Q-type Ca(2+) channels, although augmenting the levels of cAMP reveals the ability of the receptor to decrease cAMP. ..
- Orecna M, Hafko R, Toporcerová V, Strbak V, Bacova Z. Cell swelling-induced insulin secretion from INS-1E cells is inhibited by extracellular Ca2+ and is tetanus toxin resistant. Cell Physiol Biochem. 2010;26:197-208 pubmed publisher..Hypotonicity-induced insulin secretion from INS-1E cells is inhibited by extracellular Ca(2+), does not require intracellular Ca(2+) and is TeTx resistant. ..
- Bawa B, Abbott L. Analysis of calcium ion homeostasis and mitochondrial function in cerebellar granule cells of adult CaV 2.1 calcium ion channel mutant mice. Neurotox Res. 2008;13:1-18 pubmed..However, no significant differences in ROS levels were observed. It is possible that CGC death in leaner mice may be related to mitochondrial dysfunction but may not be directly related to decreased basal intracellular calcium. ..
- 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. ..
- Takamori M. What's in the serum of seronegative MG and LEMS?. Neurology. 2003;61:277; author reply 277-8 pubmed
- Goadsby P. Sporadic hemiplegic migraine: stamp collecting or food for thought?. Neurology. 2003;60:536-7 pubmed
- Takahashi E, Kajiwara N, Furuya K, Sugiyama F, Yagami K. Expression analysis of the 5'-upstream region of mouse P/Q-type Ca(2+) channel alpha( lA) subunit gene fused to Escherichia coli lacZ reporter gene in the spinal cord using transgenic mice. Neurosci Lett. 2000;284:9-12 pubmed..3-kb 5'-upstream region alone is not sufficient for the expression. ..
- Perroy J, El Far O, Bertaso F, Pin J, Betz H, Bockaert J, et al. PICK1 is required for the control of synaptic transmission by the metabotropic glutamate receptor 7. EMBO J. 2002;21:2990-9 pubmed..These results indicate that the scaffolding protein, PICK1, plays an essential role in the control of synaptic transmission by the mGlu7a receptor complex. ..
- Perroy J, Richard S, Nargeot J, Bockaert J, Fagni L. Permissive effect of voltage on mGlu 7 receptor subtype signaling in neurons. J Biol Chem. 2002;277:1223-8 pubmed..This synergistic effect of membrane depolarization and mGlu7 receptor activation provides a mechanism by which neuronal excitation could control action of the mGlu7 receptor in neurons. ..
- Campbell D, Hess E. Cerebellar circuitry is activated during convulsive episodes in the tottering (tg/tg) mutant mouse. Neuroscience. 1998;85:773-83 pubmed..These results suggest that the cerebellum, a region not classically associated with paroxysmal events, is important in the generation and/or maintenance of the intermittent convulsions in tottering mutant mice. ..
- Ishikawa T, Kaneko M, Shin H, Takahashi T. Presynaptic N-type and P/Q-type Ca2+ channels mediating synaptic transmission at the calyx of Held of mice. J Physiol. 2005;568:199-209 pubmed..These results suggest that the developmental switch of presynaptic Ca2+ channels from N- to P/Q-type may serve to increase synaptic efficacy at high frequencies of activity, securing high-fidelity synaptic transmission. ..
- Hagenacker T, Czeschik J, Schäfers M, Büsselberg D. Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-alpha. Brain Res Bull. 2010;81:157-63 pubmed publisher..5+/-7.3%). The capsaicin-induced shift towards the hyperpolarizing voltage range does not occur when TNF-alpha is applied. Summarizing, TNF-alpha sensitizes nociceptive neurons for capsaicin. ..
- Iwanami M, Odaka M, Nakamura T, Hirata K. [Paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome associated with anti P/Q-type voltage-gated calcium channel antibody in a patient with primary double lung cancer]. Brain Nerve. 2009;61:1083-7 pubmed..Physicians need to be aware that patients may develop PCD and LEMS associated with anti-VGCC antibody caused by small cell lung cancer, and a mass survey should be conducted and careful examinations performed...
- Albillos A, Neher E, Moser T. R-Type Ca2+ channels are coupled to the rapid component of secretion in mouse adrenal slice chromaffin cells. J Neurosci. 2000;20:8323-30 pubmed..Our results indicate that R-type Ca(2+) channels are in close proximity with the exocytotic machinery to rapidly regulate the secretory process. ..
- Hansen P, Jensen B, Andreasen D, Friis U, Skøtt O. Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles. Circ Res. 2000;87:896-902 pubmed
- Plomp J, van den Maagdenberg A, Molenaar P, Frants R, Ferrari M. Mutant P/Q-type calcium channel electrophysiology and migraine. Curr Opin Investig Drugs. 2001;2:1250-60 pubmed..We will review these studies and discuss the possible implications for the understanding of migraine pathophysiology. ..
- Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li S, Takei K, et al. Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J Neurosci. 2002;22:2590-7 pubmed..These results strongly suggest that Cdk5/p35 inhibits neurotransmitter release through the phosphorylation of P/Q-type VDCC and downregulation of the channel activity. ..
- Jeng C, Sun M, Chen Y, Tang C. Dominant-negative effects of episodic ataxia type 2 mutations involve disruption of membrane trafficking of human P/Q-type Ca2+ channels. J Cell Physiol. 2008;214:422-33 pubmed..Taken together, our data suggest that EA2 mutants induce significant ER retention of their wild-type counterparts, thereby suppressing the functional expression of Ca(V)2.1 channels. ..
- Kang M, Felix R, Campbell K. Long-term regulation of voltage-gated Ca(2+) channels by gabapentin. FEBS Lett. 2002;528:177-82 pubmed
- Arikkath J, Felix R, Ahern C, Chen C, Mori Y, Song I, et al. Molecular characterization of a two-domain form of the neuronal voltage-gated P/Q-type calcium channel alpha(1)2.1 subunit. FEBS Lett. 2002;532:300-8 pubmed..These studies suggest an in vivo role for the 95kD-alpha(1)2.1 in altering synaptic activity via protein-protein interactions and/or regulation of P/Q-type currents. ..
- Dobrev D, Ravens U. Therapeutically relevant concentrations of neomycin selectively inhibit P-type Ca2+ channels in rat striatum. Eur J Pharmacol. 2003;461:105-11 pubmed..In conclusion, therapeutically relevant concentrations of neomycin preferentially block P-type Ca(2+) channels which regulate dopamine release in rat striatum. This block could be responsible for aminoglycoside-induced toxicity. ..
- Womack M, Chevez C, Khodakhah K. Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons. J Neurosci. 2004;24:8818-22 pubmed..Alterations in the spontaneous activity of Purkinje neurons may be an important contributing factor to the ataxia in these subjects. ..
- Inchauspe C, Martini F, Forsythe I, Uchitel O. Functional compensation of P/Q by N-type channels blocks short-term plasticity at the calyx of Held presynaptic terminal. J Neurosci. 2004;24:10379-83 pubmed..We conclude that one physiological function of P/Q channels is to provide additional facilitatory drive, so contributing to maintenance of transmission as vesicles are depleted during high throughput synaptic transmission. ..
- Bhaukaurally K, Panatier A, Poulain D, Oliet S. Voltage-gated Ca2+ channel subtypes mediating GABAergic transmission in the rat supraoptic nucleus. Eur J Neurosci. 2005;21:2459-66 pubmed..This finding suggests that these metabotropic receptors modulate GABAergic transmission through a different mechanism, downstream of Ca2+ entry in the terminals, or upstream through the activation of K+ channels. ..