Genomes and Genes
r type calcium channels
Summary: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.
- Hajela R, Peng S, Atchison W. Comparative effects of methylmercury and Hg(2+) on human neuronal N- and R-type high-voltage activated calcium channels transiently expressed in human embryonic kidney 293 cells. J Pharmacol Exp Ther. 2003;306:1129-36 pubmed..Therefore, different types of Ca2+ channels have differential susceptibility to neurotoxic mercurials even when expressed in the same cell type. ..
- Hainsworth A, McNaughton N, Pereverzev A, Schneider T, Randall A. Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca2+ channel currents. Eur J Pharmacol. 2003;467:77-80 pubmed..Lamotrigine was also a weak inhibitor of T-type currents mediated by alpha1G subunits (<10% inhibition by 100 microM). ..
- Fang Z, Park C, Li H, Kim H, Park S, Jung S, et al. Molecular basis of Ca(v)2.3 calcium channels in rat nociceptive neurons. J Biol Chem. 2007;282:4757-64 pubmed..3e expression. Our results suggest that Ca(v)2.3e in sensory neurons may be a potential target for the treatment of pain. ..
- Kaja S, van de Ven R, Broos L, Frants R, Ferrari M, van den Maagdenberg A, et al. Characterization of acetylcholine release and the compensatory contribution of non-Ca(v)2.1 channels at motor nerve terminals of leaner Ca(v)2.1-mutant mice. Neuroscience. 2007;144:1278-87 pubmed..2 channels, and hampers that of Ca(v)2.3 channels. This is the first report directly showing at single synapses the deficits and plasticity in transmitter release resulting from the Ln mutation of Cacna1a...
- Xu H, Zhao J, Yang X. Cholinergic and dopaminergic amacrine cells differentially express calcium channel subunits in the rat retina. Neuroscience. 2003;118:763-8 pubmed..No alpha(1D) labeling was seen. These results suggest that Ca(2+) channel subunits differentially expressed on the cholinergic and dopaminergic amacrine cells may endow these two cell types with different physiological properties. ..
- Yasuda T, Lewis R, Adams D. Overexpressed Ca(v)beta3 inhibits N-type (Cav2.2) calcium channel currents through a hyperpolarizing shift of ultra-slow and closed-state inactivation. J Gen Physiol. 2004;123:401-16 pubmed
- Yang S, Berggren P. CaV2.3 channel and PKClambda: new players in insulin secretion. J Clin Invest. 2005;115:16-20 pubmed
- Peng H, Xie D, Xiao Z, Wu W, Chen Y, Xia K. [Subunit of voltage-dependent calcium channels in the murine spiral ganglion cells]. Zhonghua Er Bi Yan Hou Ke Za Zhi. 2004;39:385-8 pubmed..And the coexpression of alpha1D and alpha1 E demonstrate the presence of L-type and R-type calcium channels in mammalian spiral ganglion cells. ..
- Benquet P, Pichon Y, Tiaho F. In vitro development of P- and R-like calcium currents in insect (Periplaneta americana) embryonic brain neurons. Neurosci Lett. 2004;365:228-32 pubmed..The origin and functional implications of these modifications are discussed. ..
- Latour I, Hamid J, Beedle A, Zamponi G, MacVicar B. Expression of voltage-gated Ca2+ channel subtypes in cultured astrocytes. Glia. 2003;41:347-53 pubmed..Overall, our data indicate that astrocytes express multiple types of voltage-gated Ca(2+) channels, hinting at a complex regulation of Ca(2+) homeostasis in glial cells. ..
- Muller Y, Hanson R, Zimmerman C, Harper I, Sutherland J, Kobes S, et al. Variants in the Ca V 2.3 (alpha 1E) subunit of voltage-activated Ca2+ channels are associated with insulin resistance and type 2 diabetes in Pima Indians. Diabetes. 2007;56:3089-94 pubmed..A functional variant in CACNA1E contributes to type 2 diabetes susceptibility by affecting insulin action. This variant partially explains the linkage to type 2 diabetes on chromosome 1q21-25 in Pima Indians. ..
- Ishiguro M, Murakami K, Link T, Zvarova K, Tranmer B, Morielli A, et al. Acute and chronic effects of oxyhemoglobin on voltage-dependent ion channels in cerebral arteries. Acta Neurochir Suppl. 2008;104:99-102 pubmed..These actions of oxyhemoglobin may contribute to the development of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. ..
- Joksovic P, Weiergräber M, Lee W, Struck H, Schneider T, Todorovic S. Isoflurane-sensitive presynaptic R-type calcium channels contribute to inhibitory synaptic transmission in the rat thalamus. J Neurosci. 2009;29:1434-45 pubmed publisher..Because the thalamus has a key function in processing sensory information, sleep, and cognition, modulation of its GABAergic tone by presynaptic R-type Ca(2+) channels may contribute to the clinical effects of general anesthesia. ..
- Wang D, Yan B, Rajapaksha W, Fisher T. The expression of voltage-gated ca2+ channels in pituicytes and the up-regulation of L-type ca2+ channels during water deprivation. J Neuroendocrinol. 2009;21:858-66 pubmed publisher..Our results suggest that Ca2+ channels may play important roles in pituicyte function, including a contribution to the adaptation that occurs in pituicytes when the need for hormone release is elevated. ..
- Arnhold S, Andressen C, Angelov D, Vajna R, Volsen S, Hescheler J, et al. Embryonic stem-cell derived neurones express a maturation dependent pattern of voltage-gated calcium channels and calcium-binding proteins. Int J Dev Neurosci. 2000;18:201-12 pubmed
- Nakamura Y, Miura S, Yoshida T, Kim J, Sasaki K. Cytosolic calcium elevation induced by orexin/hypocretin in granule cell domain cells of the rat cochlear nucleus in vitro. Peptides. 2010;31:1579-88 pubmed publisher..The results further support the hypothesis that the orexin system participates in integrating neural systems that are involved in arousal, sensory processing, energy homeostasis and autonomic function. ..
- Chung G, Rhee J, Jung S, Kim J, Oh S. Modulation of CaV2.3 calcium channel currents by eugenol. J Dent Res. 2008;87:137-41 pubmed..The results indicate that eugenol has mechanisms distinct from those of capsaicin for modulating Ca(V)2.3 channels. We suggest that inhibition of Ca(V)2.3 channels by eugenol might contribute to its analgesic effect. ..
- Belardetti F, Tringham E, Eduljee C, Jiang X, Dong H, Hendricson A, et al. A fluorescence-based high-throughput screening assay for the identification of T-type calcium channel blockers. Assay Drug Dev Technol. 2009;7:266-80 pubmed publisher..This method has the potential for applications in high-throughput fluorometric imaging plate reader (FLIPR(R), Molecular Devices, Sunnyvale, CA) formats with cell lines expressing either recombinant or endogenous T-type Ca(2+) channels. ..
- Ishiguro M, Wellman T, Honda A, Russell S, Tranmer B, Wellman G. Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage. Circ Res. 2005;96:419-26 pubmed..2 and CaV 2.3. We propose that R-type VDCCs may contribute to enhanced cerebral artery constriction after SAH and may represent a novel therapeutic target in the treatment of neurological deficits after SAH. ..
- Nonaka K, Murayama N, Maeda M, Shoudai K, Shin M, Akaike N. P- and R-type Ca2+ channels regulating spinal glycinergic nerve terminals. Toxicon. 2010;55:1283-90 pubmed publisher..Overall, our results suggest that the dominant control of glycine release depends on Ca2+ entry through P- and R-type Ca2+ channels that ubiquitously populate spinal glycine release sites. ..
- McNaughton N, Davies C, Randall A. Inhibition of alpha(1E) Ca(2+) channels by carbonic anhydrase inhibitors. J Pharmacol Sci. 2004;95:240-7 pubmed..Topiramate (10 microM), an anticonvulsant with CAI activity, inhibited these currents by 68 +/- 7%. This off-target activity of CAIs at VSCCs may contribute to some of the effects they produce both in vitro and in vivo. ..
- Williams M, Marubio L, Deal C, Hans M, Brust P, Philipson L, et al. Structure and functional characterization of neuronal alpha 1E calcium channel subtypes. J Biol Chem. 1994;269:22347-57 pubmed..Thus, alpha 1E-mediated Ca2+ channels appear to be a pharmacologically distinct class of voltage-activated Ca2+ channels. ..
- Schneider T, Wei X, Olcese R, Costantin J, Neely A, Palade P, et al. Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit. Receptors Channels. 1994;2:255-70 pubmed..1% crude funnel web spider venom and 100% by Ni2+ (IC50 = 30 nM). Single-channel records show a complex activity pattern with several apparent conductance states, the largest having a conductance of 14 pS. ..
- Aldea M, Jun K, Shin H, Andres Mateos E, Solís Garrido L, Montiel C, et al. A perforated patch-clamp study of calcium currents and exocytosis in chromaffin cells of wild-type and alpha(1A) knockout mice. J Neurochem. 2002;81:911-21 pubmed..This may be due to altered Ca(2+) homeostasis in these mice, as compared to wild mouse chromaffin cells. ..
- Göpel S, Zhang Q, Eliasson L, Ma X, Galvanovskis J, Kanno T, et al. Capacitance measurements of exocytosis in mouse pancreatic alpha-, beta- and delta-cells within intact islets of Langerhans. J Physiol. 2004;556:711-26 pubmed
- Peng S, Hajela R, Atchison W. Characteristics of block by Pb2+ of function of human neuronal L-, N-, and R-type Ca2+ channels transiently expressed in human embryonic kidney 293 cells. Mol Pharmacol. 2002;62:1418-30 pubmed..Several Ca(2+) channel phenotypes are quite sensitive to the inhibitory action of Pb(2+). Furthermore, it seems that Pb(2+) is more likely to combine with Ca(2+) channels in the closed state. ..
- Dietrich D, Kirschstein T, Kukley M, Pereverzev A, von der Brelie C, Schneider T, et al. Functional specialization of presynaptic Cav2.3 Ca2+ channels. Neuron. 2003;39:483-96 pubmed
- Lee S, Choi S, Lee T, Kim H, Chin H, Shin H. Molecular basis of R-type calcium channels in central amygdala neurons of the mouse. Proc Natl Acad Sci U S A. 2002;99:3276-81 pubmed..These latter findings imply a possible role of alpha1E-based R-type Ca2+ currents in amygdala physiology associated with fear. ..
- Matsuda Y, Saegusa H, Zong S, Noda T, Tanabe T. Mice lacking Ca(v)2.3 (alpha1E) calcium channel exhibit hyperglycemia. Biochem Biophys Res Commun. 2001;289:791-5 pubmed..These results suggest that Ca(v)2.3 channel plays a role in glucose homeostasis by reducing insulin sensitivity and that Ca(v)2.3-/- mice exhibit symptoms resembling non-insulin-dependent diabetes mellitus. ..
- Gasparini S, Kasyanov A, Pietrobon D, Voronin L, Cherubini E. Presynaptic R-type calcium channels contribute to fast excitatory synaptic transmission in the rat hippocampus. J Neurosci. 2001;21:8715-21 pubmed..These channels are involved in fast glutamatergic transmission at hippocampal synapses. ..
- Kamatchi G, Franke R, Lynch C, Sando J. Identification of sites responsible for potentiation of type 2.3 calcium currents by acetyl-beta-methylcholine. J Biol Chem. 2004;279:4102-9 pubmed..3 channels to MCh. Because Cav 2.3 channels contribute to action potential-induced Ca2+ influx, these sites may account for M1 receptor-mediated regulation of neurotransmission at some synapses. ..
- Watanabe M, Sakuma Y, Kato M. High expression of the R-type voltage-gated Ca2+ channel and its involvement in Ca2+-dependent gonadotropin-releasing hormone release in GT1-7 cells. Endocrinology. 2004;145:2375-83 pubmed..The R- and L-type Ca(2+) channels play a critical role in the regulation of Ca(2+)-dependent GnRH release. ..
- Isomura Y, Fujiwara Tsukamoto Y, Imanishi M, Nambu A, Takada M. Distance-dependent Ni(2+)-sensitivity of synaptic plasticity in apical dendrites of hippocampal CA1 pyramidal cells. J Neurophysiol. 2002;87:1169-74 pubmed..The differentially distributed calcium channels may play a critical role in the induction of LTP at dendritic synapses of the hippocampal pyramidal cells...
- Toriyama H, Wang L, Saegusa H, Zong S, Osanai M, Murakoshi T, et al. Role of Ca(v) 2.3 (alpha1E ) Ca2+ channel in ischemic neuronal injury. Neuroreport. 2002;13:261-5 pubmed..These results suggest that the Ca(v)2.3 channel plays a protective role in ischemic neuronal injury by a mechanism in which GABAergic neuronal actions are involved. ..
- Pereverzev A, Mikhna M, Vajna R, Gissel C, Henry M, Weiergräber M, et al. Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(v)2.3 (alpha 1E) subunit of voltage-gated Ca(2+) channels. Mol Endocrinol. 2002;16:884-95 pubmed..3-deficient mice has dual components related to endocrine and neurological defects. The present findings provide direct evidence of a functional role for the Ca(v)2.3 subunit in hormone secretion and glucose homeostasis. ..
- Pereverzev A, Vajna R, Pfitzer G, Hescheler J, Klockner U, Schneider T. Reduction of insulin secretion in the insulinoma cell line INS-1 by overexpression of a Ca(v)2.3 (alpha1E) calcium channel antisense cassette. Eur J Endocrinol. 2002;146:881-9 pubmed..alpha1E is involved in glucose-induced insulin secretion probably by influencing the excitability of INS-1 cells. ..
- Bender K, Trussell L. Axon initial segment Ca2+ channels influence action potential generation and timing. Neuron. 2009;61:259-71 pubmed publisher..Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca(2+) channels at the site of spike initiation play a key role in generating and shaping spike bursts. ..
- Brevi S, De Curtis M, Magistretti J. Pharmacological and biophysical characterization of voltage-gated calcium currents in the endopiriform nucleus of the guinea pig. J Neurophysiol. 2001;85:2076-87 pubmed
- Berrou L, Klein H, Bernatchez G, Parent L. A specific tryptophan in the I-II linker is a key determinant of beta-subunit binding and modulation in Ca(V)2.3 calcium channels. Biophys J. 2002;83:1429-42 pubmed..Altogether these results suggest that W386 is critical for beta-subunit binding and modulation of HVA Ca(2+) channels. ..
- Giovannini F, Sher E, Webster R, Boot J, Lang B. Calcium channel subtypes contributing to acetylcholine release from normal, 4-aminopyridine-treated and myasthenic syndrome auto-antibodies-affected neuromuscular junctions. Br J Pharmacol. 2002;136:1135-45 pubmed..4 Altogether, these data demonstrate that multiple VDCC subtypes are present at the mouse NMJ and that a resistant component can be identified under 'pharmacological' and/or 'pathological' conditions. ..
- Meacham C, White L, Barone S, Shafer T. Ontogeny of voltage-sensitive calcium channel alpha(1A) and alpha(1E) subunit expression and synaptic function in rat central nervous system. Brain Res Dev Brain Res. 2003;142:47-65 pubmed..Overall, the results suggest that expression of voltage-sensitive Ca(2+) channels during development is dynamic and is important in central nervous system development. ..
- Liang H, DeMaria C, Erickson M, Mori M, Alseikhan B, Yue D. Unified mechanisms of Ca2+ regulation across the Ca2+ channel family. Neuron. 2003;39:951-60 pubmed
- Weiergräber M, Kamp M, Radhakrishnan K, Hescheler J, Schneider T. The Ca(v)2.3 voltage-gated calcium channel in epileptogenesis--shedding new light on an enigmatic channel. Neurosci Biobehav Rev. 2006;30:1122-44 pubmed..3 in etiology and pathogenesis of human epileptic syndromes as well as development of new antiepileptic drugs specifically targeting Ca(v)2.3 turns out to become indispensable. ..
- Metz A, Jarsky T, Martina M, Spruston N. R-type calcium channels contribute to afterdepolarization and bursting in hippocampal CA1 pyramidal neurons. J Neurosci. 2005;25:5763-73 pubmed..Because the ADP correlates directly with burst firing in CA1 neurons, R-type calcium channels are crucial to this important cellular behavior, which is known to encode hippocampal place fields and enhance synaptic plasticity. ..
- Takahashi E, Nagasu T. Expression pattern of voltage-dependent calcium channel alpha1 and beta subunits in adrenal gland of N-type Ca2+ channel alpha1B subunit gene-deficient mice. Mol Cell Biochem. 2005;271:91-9 pubmed..3-kb 5'-upstream region of alpha1A gene contains enhancer cis-element(s) for compensation in adrenal medulla chromaffin cells. ..
- Breustedt J, Vogt K, Miller R, Nicoll R, Schmitz D. Alpha1E-containing Ca2+ channels are involved in synaptic plasticity. Proc Natl Acad Sci U S A. 2003;100:12450-5 pubmed..Indeed, optical recordings directly show the presence and the function of alpha1E-containing VDCCs at mossy fiber terminals. Hence, a previously undescribed role for alpha1E-containing VDCCs is suggested by these results. ..
- Vacas J, Fernandez M, Ros M, Blanco P. Adenosine modulation of [Ca2+]i in cerebellar granular cells: multiple adenosine receptors involved. Brain Res. 2003;992:272-80 pubmed..These results suggest that adenosine modulate [Ca(2+)](i) in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels. ..
- 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. ..
- Pagani R, Song M, McEnery M, Qin N, Tsien R, Toro L, et al. Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse. Neuroscience. 2004;123:75-85 pubmed
- Bannister R, Melliti K, Adams B. Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors. Mol Pharmacol. 2004;65:381-8 pubmed