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Br J Pharmacol
2012 Mar 01;1655:1572-83. doi: 10.1111/j.1476-5381.2011.01646.x.
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A β-amyloid oligomer directly modulates P/Q-type calcium currents in Xenopus oocytes.
Mezler M
,
Barghorn S
,
Schoemaker H
,
Gross G
,
Nimmrich V
.
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β-amyloid (Aβ) oligomers have been implicated in the early pathophysiology of Alzheimer's disease (AD). While the precise nature of the molecular target has not been fully revealed, a number of studies have indicated that Aβ oligomers modulate neuron-specific ion channels. We recently provided evidence that Aβ oligomers suppress isolated P/Q-type calcium currents in cultured nerve cells. Using a heterologous expression system, we aimed to prove a direct effect on the membrane channel mediating such current.The effects of a synthetically generated Aβ oligomer, Aβ globulomer, were investigated on P/Q-type currents recorded from Xenopus laevis oocytes expressing the full P/Q-type calcium channel or the pore-forming subunit only. We also examined the effects of Aβ globulomer on recombinant NMDA receptor currents. Finally, we compared the modulation by Aβ globulomer with that induced by a synthetic monomeric Aβ.Aβ globulomer directly and dose-dependently modulated P/Q-type calcium channels. A leftward shift of the current-voltage curve indicated that the threshold for channel opening was reduced. The effect of Aβ globulomer was also present when only the α1A subunit of the normally tripartite channel was expressed. In contrast, the monomeric Aβ had no effect on P/Q current. Also globulomer Aβ had no effect on glutamate-induced NMDA currents.The α1A subunit of the P/Q-type calcium channel is directly modulated by oligomeric Aβ. Threshold reduction as well as an increase in current at synaptic terminals may facilitate vesicle release and could trigger excitotoxic events in the brains of patients with AD.
Abramov,
Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses.
2009, Pubmed
Abramov,
Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses.
2009,
Pubmed
Barghorn,
Globular amyloid beta-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease.
2005,
Pubmed
Buckingham,
Oocytes as an expression system for studying receptor/channel targets of drugs and pesticides.
2006,
Pubmed
,
Xenbase
Buraei,
The separation of antagonist from agonist effects of trisubstituted purines on CaV2.2 (N-type) channels.
2008,
Pubmed
,
Xenbase
Cleary,
Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function.
2005,
Pubmed
De Felice,
Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine.
2007,
Pubmed
Evans,
Presynaptic Ca2+ channels--integration centers for neuronal signaling pathways.
2006,
Pubmed
Haass,
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.
2007,
Pubmed
Harkany,
beta-amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis.
2000,
Pubmed
Hillen,
Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies.
2010,
Pubmed
Ittner,
Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models.
2010,
Pubmed
Kass,
Voltage-dependent modulation of cardiac calcium channel current by optical isomers of Bay K 8644: implications for channel gating.
1987,
Pubmed
Kelly,
beta-Amyloid-induced dynamin 1 degradation is mediated by N-methyl-D-aspartate receptors in hippocampal neurons.
2006,
Pubmed
Kelly,
Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal neurons.
2007,
Pubmed
Koch,
The binding of kappa-Conotoxin PVIIA and fast C-type inactivation of Shaker K+ channels are mutually exclusive.
2004,
Pubmed
,
Xenbase
Lacor,
Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease.
2007,
Pubmed
Lambert,
Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins.
1998,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase
Mezler,
Inhibitors of GlyT1 affect glycine transport via discrete binding sites.
2008,
Pubmed
,
Xenbase
Mezler,
Cloning and functional expression of GABA(B) receptors from Drosophila.
2001,
Pubmed
,
Xenbase
Molnár,
Enhancement of NMDA responses by beta-amyloid peptides in the hippocampus in vivo.
2004,
Pubmed
Moreno,
beta subunits influence the biophysical and pharmacological differences between P- and Q-type calcium currents expressed in a mammalian cell line.
1997,
Pubmed
Nimmrich,
Amyloid beta oligomers (A beta(1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents.
2008,
Pubmed
Puzzo,
Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus.
2008,
Pubmed
Sather,
Distinctive biophysical and pharmacological properties of class A (BI) calcium channel alpha 1 subunits.
1993,
Pubmed
,
Xenbase
Schreibmayer,
Kinetic modulation of guinea-pig cardiac L-type calcium channels by fendiline and reversal of the effects of Bay K 8644.
1992,
Pubmed
Shankar,
Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway.
2007,
Pubmed
Sills,
The mechanisms of action of gabapentin and pregabalin.
2006,
Pubmed
Soong,
Systematic identification of splice variants in human P/Q-type channel alpha1(2.1) subunits: implications for current density and Ca2+-dependent inactivation.
2002,
Pubmed
Stea,
Localization and functional properties of a rat brain alpha 1A calcium channel reflect similarities to neuronal Q- and P-type channels.
1994,
Pubmed
,
Xenbase
Sutton,
Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones.
2002,
Pubmed
Tedford,
Direct G protein modulation of Cav2 calcium channels.
2006,
Pubmed
Texidó,
Amyloid β peptide oligomers directly activate NMDA receptors.
2011,
Pubmed
,
Xenbase
Trommer,
ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.
2005,
Pubmed
Tsunemi,
Novel Cav2.1 splice variants isolated from Purkinje cells do not generate P-type Ca2+ current.
2002,
Pubmed
Verdoorn,
Rat brain N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
1987,
Pubmed
,
Xenbase
Walsh,
Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo.
2002,
Pubmed
Walsh,
Deciphering the molecular basis of memory failure in Alzheimer's disease.
2004,
Pubmed
Walsh,
Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation.
2005,
Pubmed
Wang,
Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5.
2004,
Pubmed
Wei,
Pharmacologic and radioligand binding analysis of the actions of 1,4-dihydropyridine activator-antagonist pairs in smooth muscle.
1986,
Pubmed
