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

Resumen:
Xenopus laevis oocytes exposed to amyloid-beta 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 mu M 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 (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 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.

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