omega conotoxin gvia


Summary: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.

Top Publications

  1. Williams M, Brust P, Feldman D, Patthi S, Simerson S, Maroufi A, et al. Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. Science. 1992;257:389-95 pubmed
    ..The heterogeneity of alpha 1B subunits, along with the heterogeneity of alpha 2 and beta subunits, is consistent with multiple, biophysically distinct N-type calcium channels. ..
  2. Matthews E, Dickenson A. Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy. Pain. 2001;92:235-46 pubmed
    ..This indicates an altered role for N-type but not P-type VDCCs in sensory transmission after neuropathy and selective plasticity in these channels after nerve injury. Both pre- and post-synaptic VDCCs appear to be important. ..
  3. Scott D, Wright C, Angus J. Actions of intrathecal omega-conotoxins CVID, GVIA, MVIIA, and morphine in acute and neuropathic pain in the rat. Eur J Pharmacol. 2002;451:279-86 pubmed
    ..Omega-conotoxin CVID had similar potency to omega-conotoxin MVIIA but showed less toxicity in the therapeutic range. ..
  4. Su X, Leon L, Laping N. Role of spinal Cav2.2 and Cav2.1 ion channels in bladder nociception. J Urol. 2008;179:2464-9 pubmed publisher
    ..However, agatoxin and verapamil were less effective. The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role. ..
  5. Urbano F, Depetris R, Uchitel O. Coupling of L-type calcium channels to neurotransmitter release at mouse motor nerve terminals. Pflugers Arch. 2001;441:824-31 pubmed
    ..In summary, our results show coupling of L-type VDCC to neurotransmitter release when protein phosphatases are inhibited and intracellular [Ca2+] is buffered by the fast chelator BAPTA. ..
  6. Easter A, Spruce A. Recombinant GABA(B) receptors formed from GABA(B1) and GABA(B2) subunits selectively inhibit N-type Ca(2+) channels in NG108-15 cells. Eur J Pharmacol. 2002;440:17-25 pubmed
    ..In fact, in differentiated NG108-15 cells, the recombinant GABA(B) receptors couple only to N-type Ca(2+) channels. ..
  7. Wu S, Chen H, Liu Y, Chiang H. Block of L-type Ca2+ current by beauvericin, a toxic cyclopeptide, in the NG108-15 neuronal cell line. Chem Res Toxicol. 2002;15:854-60 pubmed
    ..Under current-clamp configuration, beauvericin reduced the firing frequency of action potentials. Therefore, this study indicates that beauvericin is a relatively specific inhibitor of L-type Ca2+ current in NG108-15 cells. ..
  8. Shafer T, Meacham C, Barone S. Effects of prolonged exposure to nanomolar concentrations of methylmercury on voltage-sensitive sodium and calcium currents in PC12 cells. Brain Res Dev Brain Res. 2002;136:151-64 pubmed
    ..These results demonstrate that prolonged exposure to low concentrations of CH(3)Hg(+) reduces cationic currents in differentiating PC12 cells, but that current reduction is not always associated with morphological alteration...
  9. Hampson R, Zhuang S, Weiner J, Deadwyler S. Functional significance of cannabinoid-mediated, depolarization-induced suppression of inhibition (DSI) in the hippocampus. J Neurophysiol. 2003;90:55-64 pubmed
    ..Under the conditions tested, the normal firing patterns of hippocampal neurons that occur in vivo do not appear to elicit DSI. ..

More Information


  1. Jiménez González C, McLaren G, Dale N. Development of Ca2+-channel and BK-channel expression in embryos and larvae of Xenopus laevis. Eur J Neurosci. 2003;18:2175-87 pubmed
    ..The newly expressed P/Q channels play a role in spike initiation and repetitive firing in larval spinal neurons and contribute to burst generation during swimming in the larva. ..
  2. Kitagawa H, Akiyama T, Yamazaki T. Myocardial interstitial noradrenaline monitoring during occlusion of inferior vena cava in cats. Acta Physiol Scand. 1998;163:173-9 pubmed
  3. Nudler S, Pagani M, Urbano F, McEnery M, Uchitel O. Testosterone modulates Ca(v2.2) calcium channels' functional expression at rat levator ani neuromuscular junction. Neuroscience. 2005;134:817-26 pubmed
    ..2) and transmitter release at the neuromuscular junctions of these sexually dimorphic motoneurons. ..
  4. 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. ..
  5. Zygmunt P, Zygmunt P, Högestätt E, Andersson K. Effects of omega-conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor. Br J Pharmacol. 1993;110:1285-90 pubmed
    ..This raises the question whether VOCCs of a type other than L, T, and N is involved in the mediation of this response. ..
  6. Santafe M, Salon I, Garcia N, Lanuza M, Uchitel O, Tomas J. Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult rat. Eur J Neurosci. 2003;17:119-27 pubmed
    ..We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse. ..
  7. Chen W, Kirchgessner A. Activation of group II mGlu receptors inhibits voltage-gated Ca2+ currents in myenteric neurons. Am J Physiol Gastrointest Liver Physiol. 2002;283:G1282-9 pubmed
    ..Inhibition of N-type calcium channels produced by activation of group II mGlu receptors may modulate enteric neurotransmission. ..
  8. Yarotskyy V, Elmslie K. Interference between two modulators of N-type (CaV2.2) calcium channel gating demonstrates that omega-conotoxin GVIA disrupts open state gating. Biochim Biophys Acta. 2010;1798:1821-8 pubmed publisher
    ..By strongly limiting access to the N-channel open state, GVIA analogs that selectively induce this modulation could provide the basis for the next generation drugs that treat chronic pain. ..
  9. Gasior M, White N, Rogawski M. Prolonged attenuation of amygdala-kindled seizure measures in rats by convection-enhanced delivery of the N-type calcium channel antagonists omega-conotoxin GVIA and omega-conotoxin MVIIA. J Pharmacol Exp Ther. 2007;323:458-68 pubmed
  10. Li W, Thaler C, Brehm P. Calcium channels in Xenopus spinal neurons differ in somas and presynaptic terminals. J Neurophysiol. 2001;86:269-79 pubmed
  11. Satoh E, Shimeki S. Acute restraint stress enhances calcium mobilization and glutamate exocytosis in cerebrocortical synaptosomes from mice. Neurochem Res. 2010;35:693-701 pubmed publisher
    ..These results indicate that acute restraint stress enhances K(+)- or 4-AP-induced glutamate release by increasing [Ca(2+)](i) via stimulation of Ca(2+) entry through P- and N-type Ca(2+) channels...
  12. Akaishi T, Nakazawa K, Sato K, Saito H, Ohno Y, Ito Y. Modulation of voltage-gated Ca2+ current by 4-hydroxynonenal in dentate granule cells. Biol Pharm Bull. 2004;27:174-9 pubmed
    ..These results suggest that 4HN modulates L-type Ca2+ channels in the dentate granule cells, and thereby plays a role in the physiological and pathophysiological responses of these cells to oxidative stress. ..
  13. Tokunaga T, Miyazaki K, Koseki M, Mobarakeh J, Ishizuka T, Yawo H. Pharmacological dissection of calcium channel subtype-related components of strontium inflow in large mossy fiber boutons of mouse hippocampus. Hippocampus. 2004;14:570-85 pubmed
    ..Almost similar results were observed for Ca2+ inflow-dependent fluorescence increments. L-type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials. ..
  14. McMillian M, Tuominen R, Hudson P, Suh H, Hong J. Angiotensin II receptors are coupled to omega-conotoxin-sensitive calcium influx in bovine adrenal medullary chromaffin cells. J Neurochem. 1992;58:1285-91 pubmed
    ..This study shows that AII receptors, but not bradykinin receptors, are linked to an omega Cgtx-sensitive Ca2+ influx pathway in BAM cells. ..
  15. Fredholm B. Differential sensitivity to blockade by 4-aminopyridine of presynaptic receptors regulating [3H]acetylcholine release from rat hippocampus. J Neurochem. 1990;54:1386-90 pubmed
    ..Furthermore, the results indicate that presynaptic A1 receptors on hippocampal cholinergic neurons do not primarily regulate 4-AP-dependent potassium channels, but that they might act directly on a Ca2+ conductance. ..
  16. Ichida S, Wada T, Hashimoto K, Kasamatsu Y, Akimoto T, Tahara M. Binding and labeling of omega-conotoxin GVIA in crude membranes from subfractionated fractions and various areas of chick brain. Neurochem Res. 1996;21:675-80 pubmed
  17. Brock J, Cunnane T, Ziogas J. Local application of omega-conotoxin GVIA to sympathetic nerve terminals in the guinea-pig isolated vas deferens. Br J Pharmacol. 1989;98 Suppl:775P pubmed
    ..Electron micrographs showed an alteration of the staphylococcal cell wall after clindamycin treatment. ..
  18. Maggi C, Patacchini R, Santicioli P, Lippe I, Giuliani S, Geppetti P, et al. The effect of omega conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1988;338:107-13 pubmed
    ..5. In the rat isolated proximal duodenum, field stimulation in the presence of atropine and guanethidine produced a primary relaxation followed by a rebound contraction.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  19. De Luca A, Li C, Rand M, Reid J, Thaina P, Wong Dusting H. Effects of omega-conotoxin GVIA on autonomic neuroeffector transmission in various tissues. Br J Pharmacol. 1990;101:437-47 pubmed
  20. Tanaka Y, Ando S. Age-related changes in the subtypes of voltage-dependent calcium channels in rat brain cortical synapses. Neurosci Res. 2001;39:213-20 pubmed
    ..These changes in VDCCs may lead to age-related hypofunction of synaptic neurotransmission in brain cortices. ..
  21. Wilson S, Toth P, Oh S, Gillard S, Volsen S, Ren D, et al. The status of voltage-dependent calcium channels in alpha 1E knock-out mice. J Neurosci. 2000;20:8566-71 pubmed
    ..We conclude that there exists a component of the R current that results from the expression of the alpha(1E) Ca channel subunit but that the majority of R currents must result from the expression of other Ca channel alpha subunits. ..
  22. Ichida S, Abe J, Komoike K, Imanishi T, Wada T, Masuko T, et al. Characteristics of omega-conotoxin GVI A and MVIIC binding to Cav 2.1 and Cav 2.2 channels captured by anti-Ca2+ channel peptide antibodies. Neurochem Res. 2005;30:457-66 pubmed
  23. Wada T, Imanishi T, Kawaguchi A, Mori M, Mori Y, Imoto K, et al. Effects of calmodulin and Ca2+ channel blockers on omega-conotoxin GVIA binding to crude membranes from alpha1B subunit (Cav2.2) expressed BHK cells and mice brain lacking the alpha1B subunits. Neurochem Res. 2005;30:1045-54 pubmed
    ..2 channels which are also inhibited by CaM and have not specific binding sites for omega-CTX MVIIC, although omega-CTX MVIIC is a blocker for both Cav2.1 (alpha1A; P/Q-type) and Cav2.2 channels. ..
  24. Zhang H, Langeslag M, Voncken M, Roubos E, Scheenen W. Melanotrope cells of Xenopus laevis express multiple types of high-voltage-activated Ca2+ channels. J Neuroendocrinol. 2005;17:1-9 pubmed
    ..The results provide the basis for future studies on the complex regulation of channel-mediated Ca2+ influxes into this neuroendocrine cell type as a function of its role in the animal's adaptation to external challenges. ..
  25. Spadoni F, Martella G, Martorana A, Lavaroni F, D Angelo V, Bernardi G, et al. Opioid-mediated modulation of calcium currents in striatal and pallidal neurons following reserpine treatment: focus on kappa response. Synapse. 2004;51:194-205 pubmed
    ..The suppression of the kappa response only in striatum reinforces the notion of an imbalance of endogenous opiates as relevant in extrapyramidal motor dysfunctions. ..
  26. Takahashi N, Aizawa H, Inoue H, Matsumoto K, Nakano H, Hirose T, et al. Effects of epinastine hydrochloride on cholinergic neuro-effector transmission in canine tracheal smooth muscle. Eur J Pharmacol. 1998;358:55-61 pubmed
  27. Just S, Leipold Büttner C, Heppelmann B. Histological demonstration of voltage dependent calcium channels on calcitonin gene-related peptide-immunoreactive nerve fibres in the mouse knee joint. Neurosci Lett. 2001;312:133-6 pubmed
    ..These data were further confirmed by identical results obtained after an immunohistochemical demonstration of the two channel subtypes at the peptidergic nerve fibres. ..
  28. Foehring R, Mermelstein P, Song W, Ulrich S, Surmeier D. Unique properties of R-type calcium currents in neocortical and neostriatal neurons. J Neurophysiol. 2000;84:2225-36 pubmed
    ..Ni(2+) sensitivity was not diagnostic for R-type currents in either cell type. Single-cell RT-PCR revealed that both cell types expressed the alpha1E mRNA, consistent with this subunit being associated with the R-type current...
  29. Kitayama M, Hirota K, Kudo M, Kudo T, Ishihara H, Matsuki A. Inhibitory effects of intravenous anaesthetic agents on K(+)-evoked glutamate release from rat cerebrocortical slices. Involvement of voltage-sensitive Ca(2+) channels and GABA(A) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2002;366:246-53 pubmed
  30. Sakata Y, Saegusa H, Zong S, Osanai M, Murakoshi T, Shimizu Y, et al. Analysis of Ca(2+) currents in spermatocytes from mice lacking Ca(v)2.3 (alpha(1E)) Ca(2+) channel. Biochem Biophys Res Commun. 2001;288:1032-6 pubmed
    ..3 channel makes no detectable contribution to the LVA Ca(2+) current in the pachytene spermatocyte. Instead, Ca(v)3 family such as Ca(v)3.1 may be the likely candidates responsible for the LVA currents in pachytene spermatocytes. ..
  31. Woo R, Park E, Shin M, Jeong M, Zhao R, Shin B, et al. Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices. Br J Pharmacol. 2002;137:1063-70 pubmed
  32. Durante P, Cardenas C, Whittaker J, Kitai S, Scroggs R. Low-threshold L-type calcium channels in rat dopamine neurons. J Neurophysiol. 2004;91:1450-4 pubmed
  33. Hurley J, Cahill A, Wang M, Fox A. Syntaxin 1A regulation of weakly inactivating N-type Ca2+ channels. J Physiol. 2004;560:351-63 pubmed
    ..Our data suggest that changes in inactivation can not explain the reduction in current amplitude produced by co-expressing syntaxin and a weakly inactivating Ca2+ channel. ..
  34. Currò D. Voltage-gated calcium channels involved in the inhibitory motor responses and vasoactive intestinal polypeptide release in the rat gastric fundus. Eur J Pharmacol. 2010;628:207-13 pubmed publisher
    ..1 channels is responsible for the EFS-induced VIP-like immunoreactivity release. In contrast, Ca(V)1 channels, novel VGCCs and/or molecular variants of VGCCs cloned to date may mediate a substantial component of the NANC relaxation. ..
  35. Chin J, Harris K, MacTavish D, Jhamandas J. Nociceptin/orphanin FQ modulation of ionic conductances in rat basal forebrain neurons. J Pharmacol Exp Ther. 2002;303:188-95 pubmed
  36. Fernandez J, Granja R, Izaguirre V, González García C, Cena V. omega-Conotoxin GVIA blocks nicotine-induced catecholamine secretion by blocking the nicotinic receptor-activated inward currents in bovine chromaffin cells. Neurosci Lett. 1995;191:59-62 pubmed
    ..The results indicate that besides the blockade of N-type voltage-dependent channels, omega-conotoxin GVIA is a potent and reversible blocker of the nicotinic receptor-induced currents in chromaffin cells. ..
  37. Kim J, Kim J, Kim J, Kim K, Kwon T, Park Y. Depletion of ATP and release of presynaptic inhibition in the CA1 region of hippocampal slices during hypoglycemic hypoxia. Neurosci Lett. 2007;411:56-60 pubmed
  38. Smyth L, Yamboliev I, Mutafova Yambolieva V. N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and beta-NAD in blood vessels. Neuropharmacology. 2009;56:368-78 pubmed publisher
    ..In contrast, ATP caused vasoconstriction in both vessels. beta-NAD and ATP may mediate disparate functions in the canine mesenteric resistive and capacitative circulations. ..
  39. Matsunaga H, Ueda H. Voltage-dependent N-type Ca2+ channel activity regulates the interaction between FGF-1 and S100A13 for stress-induced non-vesicular release. Cell Mol Neurobiol. 2006;26:237-46 pubmed
    ..4. Thus, it is suggested that the interaction between FGF-1 and S100A13 responsible for stress-induced non-vesicular release is dependent of Ca(2+)-influx through N-type Ca(2+)-channels. ..
  40. Somogyi G, Zernova G, Tanowitz M, de Groat W. Role of L- and N-type Ca2+ channels in muscarinic receptor-mediated facilitation of ACh and noradrenaline release in the rat urinary bladder. J Physiol. 1997;499 ( Pt 3):645-54 pubmed
    ..Other types of Ca2+ channels, including N-type, are involved to varying degrees in non-facilitated and facilitated release under different experimental conditions. ..
  41. Bugianesi R, Augustine P, Azer K, Dufresne C, Herrington J, Kath G, et al. A cell-sparing electric field stimulation technique for high-throughput screening of voltage-gated ion channels. Assay Drug Dev Technol. 2006;4:21-35 pubmed
    ..2 by known small molecule inhibitors. Thus, the TCLEFS system is suitable for both quantitative analysis and HTS of voltage-gated sodium and calcium channels, without the liabilities of previously reported EFS methodologies. ..
  42. Patacchini R, Santicioli P, Giuliani S, Maggi C. Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle. Eur J Pharmacol. 2005;509:171-7 pubmed
    ..We conclude that H2S either acts at TRPV1 receptorial sites unblocked by capsazepine or SB 366791, or stimulates a still unidentified transient receptor potential-like channel co-expressed with TRPV1 on sensory neurons. ..
  43. Lomax R, Herrero C, Garcia Palomero E, Garcia A, Montiel C. Capacitative Ca2+ entry into Xenopus oocytes is sensitive to omega-conotoxins GVIA, MVIIA and MVIIC. Cell Calcium. 1998;23:229-39 pubmed
    ..These findings support the hypothesis that capacitative Ca2+ entry into Xenopus oocytes occurs through channels with a pharmacology similar to that of neuronal non-L type voltage-gated Ca2+ channels. ..
  44. Varma N, Brager D, Morishita W, Lenz R, London B, Alger B. Presynaptic factors in the regulation of DSI expression in hippocampus. Neuropharmacology. 2002;43:550-62 pubmed
    ..Significant DSI of mIPSCs remained in omega-conotoxin, hence we infer that block of N-channels does not fully explain hippocampal DSI expression. ..
  45. Wright C, Robertson A, Whorlow S, Angus J. Cardiovascular and autonomic effects of omega-conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays. Br J Pharmacol. 2000;131:1325-36 pubmed
    ..This may point to subtype N-type calcium channel selectivity. ..
  46. Martire M, Altobelli D, Maurizi S, Preziosi P, Fuxe K. K(+)-Evoked [(3)H]D-aspartate release in rat spinal cord synaptosomes: modulation by neuropeptide Y and calcium channel antagonists. J Neurosci Res. 2000;62:722-9 pubmed
    ..Characterization of the receptors that can inhibit the release of glutamate may provide useful information for treatment of conditions characterized by excessive glutamatergic transmission in the spinal cord. ..
  47. McDonald R, Vaughan P, Peers C. Muscarinic (M1) receptor-mediated inhibition of K(+)-evoked [3H]-noradrenaline release from human neuroblastoma (SH-SY5Y) cells via inhibition of L- and N-type Ca2+ channels. Br J Pharmacol. 1994;113:621-7 pubmed
    ..Activation of muscarinic Ml receptors can inhibit release via a pertussis toxin-insensitive mechanism which involves non-selective inhibition of L- and N-type Ca2+ channels. ..
  48. Hernández M, Barahona M, Recio P, Bustamante S, Benedito S, Rivera L, et al. PACAP 38 is involved in the non-adrenergic non-cholinergic inhibitory neurotransmission in the pig urinary bladder neck. Neurourol Urodyn. 2006;25:490-7 pubmed
  49. Liu L, Barrett C, Rittenhouse A. Arachidonic acid both inhibits and enhances whole cell calcium currents in rat sympathetic neurons. Am J Physiol Cell Physiol. 2001;280:C1293-305 pubmed
    ..AA also enhanced the rate of N-type current activation. These findings indicate that AA causes multiple changes in sympathetic Ca(2+) currents. ..
  50. Soldo B, Moises H. mu-opioid receptor activation inhibits N- and P-type Ca2+ channel currents in magnocellular neurones of the rat supraoptic nucleus. J Physiol. 1998;513 ( Pt 3):787-804 pubmed
    ..They also support a scheme in which opioids may act in part to modulate cellular activity and regulate neurosecretory function by their direct action on the neuroendocrine neurones of the hypothalamic supraoptic neucleus. ..
  51. Momiyama T. Parallel decrease in omega-conotoxin-sensitive transmission and dopamine-induced inhibition at the striatal synapse of developing rats. J Physiol. 2003;546:483-90 pubmed
  52. Belardetti F, Ahn S, So K, Snutch T, Phillips A. Block of voltage-gated calcium channels stimulates dopamine efflux in rat mesocorticolimbic system. Neuropharmacology. 2009;56:984-93 pubmed publisher
  53. Kim E, Chang S, Chung J, Ryu B, Joo C, Moon H, et al. Attenuation of Zn2+ neurotoxicity by aspirin: role of N-type Ca2+ channel and the carboxyl acid group. Neurobiol Dis. 2001;8:774-83 pubmed
    ..The present findings suggest that aspirin prevents Zn2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group. ..