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KMID : 0578320120340040349
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Molecules and Cells
2012 Volume.34 No. 4 p.349 ~ p.355
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Functional and Structural Effects of Amyloid-β Aggregate on Xenopus laevis Oocytes
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Jorge Parodi
Lenin Ochoa-de la Paz
Ricardo Miledi
Ataulfo Martinez-Torres
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Abstract
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Xenopus laevis oocytes exposed to amyloid-? 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 ?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 (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.
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KEYWORD
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Alzheimer’s disease, ATP-currents, transient-outward chloride current, voltage-Clamp
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