title: Functional and structural effects of amyloid-β aggregate on Xenopus laevis oocytes.
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 Ca(2+) 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 Ca(2+)-dependent Cl(-) currents of oocytes, as shown by increased amplitude of the transient-outward chloride current (T(out)) 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 Ca(2+)-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.
authors.affiliation: Laboratorio de Fisiología de la Reproducción, Núcleo de Producción Alimentaria, Escuela de Medicina, Veterinaria, Universidad Católica de Temuco, Temuco, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Parodi
authors.forename: Lenin
authors.initials: L
authors.lastname: Ochoa-de la Paz
authors.forename: Ricardo
authors.initials: R
authors.lastname: Miledi
authors.forename: Ataúlfo
authors.initials: A
authors.lastname: Martínez-Torres
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D006801:Humans; D007700:Kinetics; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020836:Protein Structure, Quaternary; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002118:Calcium