omega agatoxin iva

Summary

Summary: A neuropeptide toxin from the venom of the funnel web spider, Agelenopsis aperta. It inhibits CALCIUM CHANNELS, P-TYPE by altering the voltage-dependent gating so that very large depolarizations are needed for channel opening. It also inhibits CALCIUM CHANNELS, Q-TYPE.

Top Publications

  1. Lorenzon N, Lutz C, Frankel W, Beam K. Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner. J Neurosci. 1998;18:4482-9 pubmed
    ..Thus, the leaner mutation selectively reduces P-type currents in Purkinje cells, and the alpha1A subunit and P-type current appear to be essential for normal cerebellar function. ..
  2. Rosato Siri M, Piriz J, Tropper B, Uchitel O. Differential Ca2+-dependence of transmitter release mediated by P/Q- and N-type calcium channels at neonatal rat neuromuscular junctions. Eur J Neurosci. 2002;15:1874-80 pubmed
    ..This difference could be accounted for by a differential location of these channels at the release site. In addition, our results indicate that space-time overlapping of calcium domains was required for facilitation. ..
  3. 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. ..
  4. Tringham E, Payne C, Dupere J, Usowicz M. Maturation of rat cerebellar Purkinje cells reveals an atypical Ca2+ channel current that is inhibited by omega-agatoxin IVA and the dihydropyridine (-)-(S)-Bay K8644. J Physiol. 2007;578:693-714 pubmed
    ..During maturation, there is a decrease in the size of the L-type current and an increase in the size of the atypical Ca2+ channel current. These changes may contribute to the maturation of the electrical properties of Purkinje cells. ..
  5. Yamamoto T, Sakashita Y. Differential effects of intrathecally administered N- and P-type voltage-sensitive calcium channel blockers upon two models of experimental mononeuropathy in the rat. Brain Res. 1998;794:329-32 pubmed
    ..In the PSNI model, both N-type and P-type VSCC blockers had no effect on thermal hyperalgesia. This suggests that some types of neuropathic pain may be treatable with N-type VSCC blockers. ..
  6. Momiyama T, Koga E. Dopamine D(2)-like receptors selectively block N-type Ca(2+) channels to reduce GABA release onto rat striatal cholinergic interneurones. J Physiol. 2001;533:479-92 pubmed
  7. Mesquita F, Prado M, Gomez R, Romano Silva M, Gomez M. The effect of calcium channels blockers in the K+-evoked release of [3H]adenine nucleotides from rat brain cortical synaptosomes. Neurosci Lett. 1998;258:57-9 pubmed
    ..It is concluded that Q-type calcium channels are directly involved in the release of adenine nucleotides in rat brain cortical synaptosomes. ..
  8. Chuhma N, Koyano K, Ohmori H. Synchronisation of neurotransmitter release during postnatal development in a calyceal presynaptic terminal of rat. J Physiol. 2001;530:93-104 pubmed
    ..The possible importance of developmental increases in both Ca2+ clearance capacity and Ca2+ currents is discussed in relation to the synchronisation of transmitter release. ..
  9. Saegusa H, Wakamori M, Matsuda Y, Wang J, Mori Y, Zong S, et al. Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells. Mol Cell Neurosci. 2007;34:261-70 pubmed
    ..Therefore, our results do not support the notion that the alteration of the channel properties may underlie the pathogenic mechanism of SCA6. ..

More Information

Publications62

  1. Mochida S, Few A, Scheuer T, Catterall W. Regulation of presynaptic Ca(V)2.1 channels by Ca2+ sensor proteins mediates short-term synaptic plasticity. Neuron. 2008;57:210-6 pubmed publisher
    ..Activity-dependent regulation of presynaptic Ca(V)2.1 channels by CaS proteins may therefore be a primary determinant of short-term synaptic plasticity and information-processing in the nervous system. ..
  2. 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
  3. Ohba T, Takahashi E, Murakami M. Modified autonomic regulation in mice with a P/Q-type calcium channel mutation. Biochem Biophys Res Commun. 2009;381:27-32 pubmed publisher
    ..Atrium contraction analyses revealed a minor but significant role for P/Q-type channels in sympathetic and parasympathetic nerve regulation. ..
  4. Rathmayer W, Djokaj S, Gaydukov A, Kreissl S. The neuromuscular junctions of the slow and the fast excitatory axon in the closer of the crab Eriphia spinifrons are endowed with different Ca2+ channel types and allow neuron-specific modulation of transmitter release by two neuropeptides. J Neurosci. 2002;22:708-17 pubmed
    ..The differential effects of these two peptides allows fine tuning of transmitter release at two functionally different motor neurons innervating the same muscle. ..
  5. 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...
  6. Irnaten M, Aicher S, Wang J, Venkatesan P, Evans C, Baxi S, et al. Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus. Neuroscience. 2003;116:573-82 pubmed
  7. 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. ..
  8. El Sayah M, Calixto J. New evidence on the mechanisms underlying bradykinin-mediated contraction of the pig iris sphincter in vitro. Peptides. 2003;24:1045-51 pubmed
    ..Finally, these responses are mediated by activation of both protein kinase A- and C-dependent mechanisms. ..
  9. 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. ..
  10. 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. ..
  11. Martín R, Ladera C, Bartolomé Martín D, Torres M, Sánchez Prieto J. The inhibition of release by mGlu7 receptors is independent of the Ca2+ channel type but associated to GABAB and adenosine A1 receptors. Neuropharmacology. 2008;55:464-73 pubmed publisher
    ..Thus, occlusion of the responses by the three GPCRs is independent of the Ca2+ channel type but rather, it is associated to functional mGlu7 receptors. ..
  12. Muller W, Meske V, Berlin K, Scharnagl H, Marz W, Ohm T. Apolipoprotein E isoforms increase intracellular Ca2+ differentially through a omega-agatoxin IVa-sensitive Ca2+-channel. Brain Pathol. 1998;8:641-53 pubmed
    ..This novel mechanism is discussed with respect to Alzheimer's disease, that is linked for most cases to the apoE epsilon-allelic variation (epsilon4 > epsilon3 > epsilon2). ..
  13. Hernandez Guijo J, de Pascual R, Garcia A, Gandia L. Separation of calcium channel current components in mouse chromaffin cells superfused with low- and high-barium solutions. Pflugers Arch. 1998;436:75-82 pubmed
  14. Doroshenko P, Woppmann A, Miljanich G, Augustine G. Pharmacologically distinct presynaptic calcium channels in cerebellar excitatory and inhibitory synapses. Neuropharmacology. 1997;36:865-72 pubmed
    ..The inhibitory terminals possess quite different type(s) of Ca channel. The heterogeneous distribution of Ca channel types should impart unique properties to transmitter release from the excitatory and inhibitory terminals. ..
  15. Albillos A, Garcia A, Olivera B, Gandia L. Re-evaluation of the P/Q Ca2+ channel components of Ba2+ currents in bovine chromaffin cells superfused with solutions containing low and high Ba2+ concentrations. Pflugers Arch. 1996;432:1030-8 pubmed
    ..An R-type residual current is not present in these cells. ..
  16. Kanumilli S, Tringham E, Payne C, Dupere J, Venkateswarlu K, Usowicz M. Alternative splicing generates a smaller assortment of CaV2.1 transcripts in cerebellar Purkinje cells than in the cerebellum. Physiol Genomics. 2006;24:86-96 pubmed
    ..These results expand the known diversity of CaV2.1 transcripts in cerebellar Purkinje cells, and propose the selective expression of distinct assortments of CaV2.1 transcripts in different brain neurons and species. ..
  17. 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. ..
  18. DeBock F, Kurz J, Azad S, Parsons C, Hapfelmeier G, Zieglgansberger W, et al. Alpha2-adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o-protein-mediated modulation of Ca2+-channels and inwardly rectifying K+-channels in LTD. Eur J Neurosci. 2003;17:1411-24 pubmed
  19. José O, Hernandez Hernandez O, Chirinos M, González González M, Larrea F, Almanza A, et al. Recombinant human ZP3-induced sperm acrosome reaction: evidence for the involvement of T- and L-type voltage-gated calcium channels. Biochem Biophys Res Commun. 2010;395:530-4 pubmed publisher
    ..Consistent with this, we detected in human sperm transcripts for the Ca(V)1 auxiliary subunits, alpha(2)delta, beta(1), beta(2) and beta(4), but not the neuronal specific isoforms beta(3) and gamma(2). ..
  20. Silva A, Carvalho A, Carvalho C, Malva J. Functional interaction between neuropeptide Y receptors and modulation of calcium channels in the rat hippocampus. Neuropharmacology. 2003;44:282-92 pubmed
    ..Moreover, we also show that Y1 and Y2 receptors exert their inhibitory action by directly modulating L-, N-, and P-/Q-type VGCCs, whereas the inhibition of glutamate release mediated by the Y5 receptors seems to involve P-/Q-type VGCCs. ..
  21. Stefani A, Spadoni F, Giacomini P, Lavaroni F, Bernardi G. The modulation of calcium current by GABA metabotropic receptors in a sub-population of pallidal neurons. Eur J Neurosci. 1999;11:3995-4005 pubmed
  22. Wang J, Irnaten M, Mendelowitz D. Agatoxin-IVA-sensitive calcium channels mediate the presynaptic and postsynaptic nicotinic activation of cardiac vagal neurons. J Neurophysiol. 2001;85:164-8 pubmed
    ..The postsynaptic inward current elicited by nicotine is dependent on activation of agatoxin-IVA-sensitive voltage-dependent calcium channels. ..
  23. Loechner K, Knox R, McLaughlin J, Dunlap K. Dexamethasone-mediated inhibition of calcium transients and ACTH release in a pituitary cell line (AtT-20). Steroids. 1999;64:404-12 pubmed
    ..These data suggest, therefore, that dexamethasone does, indeed, modulate calcium homeostasis in AtT-20 cells, but that this effect is not responsible for its inhibition of secretion. ..
  24. Sitges M, Guarneros A, Nekrassov V. Effects of carbamazepine, phenytoin, valproic acid, oxcarbazepine, lamotrigine, topiramate and vinpocetine on the presynaptic Ca2+ channel-mediated release of [3H]glutamate: comparison with the Na+ channel-mediated release. Neuropharmacology. 2007;53:854-62 pubmed
  25. 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. ..
  26. 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...
  27. 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. ..
  28. Depetris R, Nudler S, Uchitel O, Urbano F. Altered synaptic synchrony in motor nerve terminals lacking P/Q-calcium channels. Synapse. 2008;62:466-71 pubmed publisher
    ..Thus, these results provide insight on the mechanisms underlying several pathologies associated with P/Q type calcium channels. ..
  29. 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. ..
  30. 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
  31. Santiago A, Carvalho C, Carvalho A, Ambrósio A. Differential contribution of L-, N-, and P/Q-type calcium channels to [Ca2+]i changes evoked by kainate in hippocampal neurons. Neurochem Res. 2008;33:1501-8 pubmed publisher
    ..The results indicate that hippocampal neurons differ in what concerns their L-, N- and P/Q-type Ca(2+) channels activated by stimulation of the AMPA/kainate receptors. ..
  32. 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. ..
  33. 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. ..
  34. 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. ..
  35. Vogel S, Smith R, Baibakov B, Ikebuchi Y, Lambert N. Calcium influx is required for endocytotic membrane retrieval. Proc Natl Acad Sci U S A. 1999;96:5019-24 pubmed
    ..We conclude that calcium influx through omega-agatoxin-sensitive channels plays a key role in signaling for endocytotic membrane retrieval. ..
  36. 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. ..
  37. 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. ..
  38. Obokata K, Kamiya H, Ozawa S. Differential effects of phorbol ester on AMPA and NMDA components of excitatory postsynaptic currents in dentate neurons of rat hippocampal slices. Neurosci Res. 1997;29:171-9 pubmed
    ..These results suggest that the potentiation of the NMDA component of the EPSC by PDAc is caused partly by a postsynaptic mechanism in the dentate neurons. ..
  39. Biton B, Granger P, Depoortere H, Scatton B, Avenet P. Block of P-type Ca2+ channels by the NMDA receptor antagonist eliprodil in acutely dissociated rat Purkinje cells. Eur J Pharmacol. 1995;294:91-100 pubmed
    ..These results demonstrate that eliprodil blocks P-type Ca2+ channels in cerebellar Purkinje neurons and suggest that this property may contribute to its neuroprotective activity. ..
  40. Zhang Z, Lin H, Cao C, Khurana S, Pallone T. Voltage-gated divalent currents in descending vasa recta pericytes. Am J Physiol Renal Physiol. 2010;299:F862-71 pubmed publisher
    ..We conclude that DVR pericytes predominantly express voltage-gated divalent currents that are carried by L-type channels. ..
  41. 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
  42. Shinohara Y, Toyohira Y, Ueno S, Liu M, Tsutsui M, Yanagihara N. Effects of resveratrol, a grape polyphenol, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Biochem Pharmacol. 2007;74:1608-18 pubmed
    ..The present findings suggest that resveratrol inhibits acetylcholine-induced catecholamine secretion and synthesis through suppressing ion influx in cultured bovine adrenal medullary cells. ..
  43. Wang S, Wang K, Wang W, Sihra T. Unexpected inhibitory regulation of glutamate release from rat cerebrocortical nerve terminals by presynaptic 5-hydroxytryptamine-2A receptors. J Neurosci Res. 2006;84:1528-42 pubmed
    ..These observations invoke presynaptic inhibitory 5-HT(2A) receptor function as a potential target for drugs to mitigate the effects of excessive glutamatergic transmission. ..
  44. 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. ..
  45. Breen L, Smyth L, Yamboliev I, Mutafova Yambolieva V. beta-NAD is a novel nucleotide released on stimulation of nerve terminals in human urinary bladder detrusor muscle. Am J Physiol Renal Physiol. 2006;290:F486-95 pubmed
    ..In conclusion, we detected nerve-evoked overflow of beta-NAD+ and ADPR in HUB. The beta-NAD(+)/ADPR system may constitute a novel inhibitory extracellular nucleotide mechanism of neural control of the human bladder. ..
  46. Galindo C, Sitges M. Dihydropiridines mechanism of action in striatal isolated nerve endings: comparison with omega-agatoxin IVA. Neurochem Res. 2004;29:659-69 pubmed
    ..It is concluded that the reduction in presynaptic Na+ channel permeability might contribute to the cerebral effects of DHPs. ..
  47. Bloomquist J. Mode of action of atracotoxin at central and peripheral synapses of insects. Invert Neurosci. 2003;5:45-50 pubmed
    ..These studies demonstrate that central synaptic calcium channels underlie the action of ACTX. ACTX-dependent neuroexcitation has a number of possible mechanisms that warrant further study. ..
  48. McDonough S, Boland L, Mintz I, Bean B. Interactions among toxins that inhibit N-type and P-type calcium channels. J Gen Physiol. 2002;119:313-28 pubmed
  49. 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. ..
  50. Molderings G, Likungu J, Gothert M. N-Type calcium channels control sympathetic neurotransmission in human heart atrium. Circulation. 2000;101:403-7 pubmed
    ..This property of mibefradil is unique among the calcium channel blockers that have been or still are therapeutically applied and may considerably contribute to its slight negative chronotropic effect in vivo. ..
  51. Lin C, Huang Y, Tsai J, Gean P. Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons. Synapse. 2001;41:351-9 pubmed
    ..These results provide the first evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-mediated enhancement of I(Ca). ..
  52. Plomp J, van den Maagdenberg A, Ferrari M, Frants R, Molenaar P. Transmitter release deficits at the neuromuscular synapse of mice with mutations in the Cav2.1 (alpha1A) subunit of the P/Q-type Ca2+ channel. Ann N Y Acad Sci. 2003;998:29-32 pubmed
  53. Fukuizumi T, Ohkubo T, Kitamura K. Spinal sensitization mechanism in vincristine-induced hyperalgesia in mice. Neurosci Lett. 2003;343:89-92 pubmed
    ..A spinal glutamatergic pathway also appears to be involved in this hyperalgesia. ..