Skip to main content
SpringerLink
Log in

Functional and structural effects of amyloid-β aggregate on Xenopus laevis oocytes

Molecules and Cells volume 34, pages 349–355 (2012)Cite this article

Abstract

Xenopus laevis oocytes exposed to amyloid-β aggregate generated oscillatory electric activity (blips) that was recorded by two-microelectrode voltage-clamp. The cells exhibited a series of “spontaneous” blips ranging in amplitude from 3.8 ± 0.9 nA at the beginning of the recordings to 6.8 ± 1.7 nA after 15 min of exposure to 1 μM aggregate. These blips were similar in amplitude to those induced by the channel-forming antimicrobial agents amphotericin B (7.8 ± 1.2 nA) and gramicidin (6.3 ± 1.1 nA). The amyloid aggregate-induced currents were abolished when extracellular Ca2+ was removed from the bathing solution, suggesting a central role for this cation in generating the spontaneous electric activity. The amyloid aggregate also affected the Ca2+-dependent Cl− currents of oocytes, as shown by increased amplitude of the transient-outward chloride current (Tout) and the serum-activated, oscillatory Cl− currents. Electron microcopy revealed that amyloid aggregate induced the dissociation of the follicular cells that surround the oocyte, thus leading to a failure in the electro-chemical communication between these cells. This was also evidenced by the suppression of the oscillatory Ca2+-dependent ATP-currents, which require proper coupling between oocytes and the follicular cell layer. These observations, made using the X. laevis oocytes as a versatile experimental model, may help to understand the effects of amyloid aggregate on cellular communication.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  • Arellano, R.O., Woodward, R.M., and Miledi, R. (1996). Ion channels and membrane receptors in follicle-enclosed Xenopus oocytes. Ion Channels 4, 203–259.

    PubMed  CAS  Google Scholar 

  • Arellano, R.O., Garay, E., and Miledi, R. (1998). Cl− currents activated via purinergic receptors in Xenopus follicles. Am. J. Physiol. 274, C333–340.

    PubMed  CAS  Google Scholar 

  • Arispe, N. (2004). Architecture of the Alzheimer’s A beta P ion channel pore. J. Membr. Biol. 197, 33–48.

    Article  PubMed  CAS  Google Scholar 

  • Arispe, N., Pollard, H.B., and Rojas, E. (1994). The ability of amyloid beta-protein [A beta P (1–40)] to form Ca2+ channels provides a mechanism for neuronal death in Alzheimer’s disease. Ann. N Y Acad. Sci. 747, 256–266.

    Article  PubMed  CAS  Google Scholar 

  • Avila, M.E., Sepulveda, F.J., Burgos, C.F., Moraga-Cid, G., Parodi, J., Moon, R.T., Aguayo, L.G., Opazo, C., and De Ferrari, G.V. (2010). Canonical Wnt3a modulates intracellular calcium and enhances excitatory neurotransmission in hippocampal neurons. J. Biol. Chem. 285, 18939–18947.

    Article  PubMed  CAS  Google Scholar 

  • Bourin, M., Ripoll, N., and Dailly, E. (2003). Nicotinic receptors and Alzheimer’s disease. Curr. Med. Res. Opin. 19, 169–177.

    Article  PubMed  CAS  Google Scholar 

  • Daniels, W.M., Hendricks, J., Salie, R., and Taljaard, J.J. (2001). The role of the MAP-kinase superfamily in beta-amyloid toxicity. Metab. Brain Dis. 16, 175–185.

    Article  PubMed  CAS  Google Scholar 

  • Haass, C., and Selkoe, D.J. (2007). Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat. Rev. Mol. Cell Biol. 8, 101–112.

    Article  PubMed  CAS  Google Scholar 

  • Hsieh, H., Boehm, J., Sato, C., Iwatsubo, T., Tomita, T., Sisodia, S., and Malinow, R. (2006). AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52, 831–843.

    Article  PubMed  CAS  Google Scholar 

  • Jang, H., Zheng, J., and Nussinov, R. (2007). Models of beta-amyloid ion channels in the membrane suggest that channel formation in the bilayer is a dynamic process. Biophys. J. 93, 1938–1949.

    Article  PubMed  CAS  Google Scholar 

  • Kawahara, M., Kuroda, Y., Arispe, N., and Rojas, E. (2000). Alzheimer’s beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell line. J. Biol. Chem. 275, 14077–14083.

    Article  PubMed  CAS  Google Scholar 

  • Maccioni, R.B., Otth, C., Concha, II., and Munoz, J.P. (2001). The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer’s pathology. Eur. J. Biochem. 268, 1518–1527.

    CAS  Google Scholar 

  • Mattson, M.P., and Chan, S.L. (2001). Dysregulation of cellular calcium homeostasis in Alzheimer’s disease: bad genes and bad habits. J. Mol. Neurosci. 17, 205–224.

    Article  PubMed  CAS  Google Scholar 

  • Mezler, M., Barghorn, S., Schoemaker, H., Gross, G., and Nim-mrich, V. (2012). Abeta oligomer directly modulates P/Q-type calcium currents in Xenopus oocytes. Br. J. Pharmacol. 165, 1572–1583

    Article  PubMed  CAS  Google Scholar 

  • Miledi, R. (1982). A calcium-dependent transient outward current in Xenopus laevis oocytes. Proc. R Soc. Lond. B. Biol. Sci. 215, 491–497.

    Article  PubMed  CAS  Google Scholar 

  • Miledi, R., and Woodward, R.M. (1989). Effects of defolliculation on membrane current responses of Xenopus oocytes. J. Physiol. 416, 601–621.

    PubMed  CAS  Google Scholar 

  • Pandya, A., and Yakel, J.L. (2011). Allosteric modulator Desformylflustrabromine relieves the inhibition of alpha2beta2 and alpha4beta2 nicotinic acetylcholine receptors by beta-amyloid(1–42) peptide. J. Mol. Neurosci. 45, 42–47.

    Article  PubMed  CAS  Google Scholar 

  • Parodi, J., Sepulveda, F.J., Roa, J., Opazo, C., Inestrosa, N.C., and Aguayo, L.G. (2009). Beta-amyloid causes depletion of synaptic vesicles leading to neurotransmission failure. J. Biol. Chem. 285, 2506–2514.

    Article  PubMed  Google Scholar 

  • Quist, A., Doudevski, I., Lin, H., Azimova, R., Ng, D., Frangione, B., Kagan, B., Ghiso, J., and Lal, R. (2005). Amyloid ion channels: a common structural link for protein-misfolding disease. Proc. Natl. Acad. Sci. USA 102, 10427–10432.

    Article  PubMed  CAS  Google Scholar 

  • Reiser, G., and Miledi, R. (1989). Changes in the properties of synaptic channels opened by acetylcholine in denervated frog muscle. Brain Res. 479, 83–97.

    Article  PubMed  CAS  Google Scholar 

  • Roberson, E.D., and Mucke, L. (2006). 100 years and counting: prospects for defeating Alzheimer’s disease. Science 314, 781–784.

    Article  PubMed  Google Scholar 

  • Saldana, C., Garay, E., Rangel, G.E., Reyes, L.M., and Arellano, R.O. (2009). Native ion current coupled to purinergic activation via basal and mechanically induced ATP release in Xenopus follicles. J. Cell. Physiol. 218, 355–365.

    Article  PubMed  CAS  Google Scholar 

  • Schroeder, B.C., Cheng, T., Jan, Y.N., and Jan, L.Y. (2008). Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 134, 1019–1029.

    Article  PubMed  CAS  Google Scholar 

  • Scudieri, P., Sondo, E., Ferrera, L., and Galietta, L.J. (2012). The anoctamin family: TMEM16A and TMEM16B as calcium-activated chloride channels. Exp. Physiol. 97, 177–183.

    Article  PubMed  CAS  Google Scholar 

  • Selkoe, D.J. (2002). Alzheimer’s disease is a synaptic failure. Science 298, 789–791.

    Article  PubMed  CAS  Google Scholar 

  • Sepulveda, F.J., Parodi, J., Peoples, R.W., Opazo, C., and Aguayo, L.G. (2010). Synaptotoxicity of Alzheimer beta amyloid can be explained by its membrane perforating property. PLoS One 5, e11820.

    Article  PubMed  Google Scholar 

  • Shankar, G.M., Bloodgood, B.L., Townsend, M., Walsh, D.M., Selkoe, D.J., and Sabatini, B.L. (2007). Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci. 27, 2866–2875.

    Article  PubMed  CAS  Google Scholar 

  • Texido, L., Martin-Satue, M., Alberdi, E., Solsona, C., and Matute, C. (2011). Amyloid beta peptide oligomers directly activate NMDA receptors. Cell Calcium 49, 184–190.

    Article  PubMed  CAS  Google Scholar 

  • Tigyi, G., Henschen, A., and Miledi, R. (1991). A factor that activates oscillatory chloride currents in Xenopus oocytes copurifies with a subfraction of serum albumin. J. Biol. Chem. 266, 20602–20609.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio de Fisiología de la Reproducción, Núcleo de Producción Alimentaria, Escuela de Medicina, Veterinaria, Facultad de Recursos Naturales, Universidad Católica de Temuco, Temuco, Chile

    Jorge Parodi

  2. Laboratorio de Neurobiología Molecular y Celular, Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, UNAM, Campus Juriquilla-Querétaro, México, México

    Jorge Parodi, Lenin Ochoa-de la Paz, Ricardo Miledi & Ataúlfo Martínez-Torres

Authors
  1. Jorge Parodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lenin Ochoa-de la Paz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ricardo Miledi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ataúlfo Martínez-Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ataúlfo Martínez-Torres.

About this article

Cite this article

Parodi, J., Ochoa-de la Paz, L., Miledi, R. et al. Functional and structural effects of amyloid-β aggregate on Xenopus laevis oocytes. Mol Cells 34, 349–355 (2012). https://doi.org/10.1007/s10059-012-2247-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-012-2247-8

Keywords

search

Navigation