Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 8 April 1994:
Vol. 264. no. 5156, pp. 276 - 279
DOI: 10.1126/science.8146663
Prev | Table of Contents | Next

Articles

Science, Vol 264, Issue 5156, 276-279
Copyright © 1994 by American Association for the Advancement of Science

articles

Soluble beta-amyloid induction of Alzheimer's phenotype for human fibroblast K+ channels

R Etcheberrigaray, E Ito, CS Kim, and DL Alkon

Laboratory of Adaptive Systems, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Although beta-amyloid is the main constituent of neurite plaques and may play a role in the pathophysiology of Alzheimer's disease, mechanisms by which soluble beta-amyloid might produce early symptoms such as memory loss before diffuse plaque deposition have not been implicated. Treatment of fibroblasts with beta-amyloid (10 nM) induced the same potassium channel dysfunction previously shown to occur specifically in fibroblasts from patients with Alzheimer's disease--namely, the absence of a 113-picosiemen potassium channel. A tetraethylammonium-induced increase of intracellular concentrations of calcium, [Ca2+]i, a response that depends on functional 113-picosiemen potassium channels, was also eliminated or markedly reduced by 10 nM beta-amyloid. Increased [Ca2+]i induced by high concentrations of extracellular potassium and 166-picosiemen potassium channels were unaffected by 10 nM beta-amyloid. In Alzheimer's disease, then, beta-amyloid might alter potassium channels and thus impair neuronal function to produce symptoms such as memory loss by a means other than plaque formation.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil.
B. Sharma, N. Singh, and M. Singh (2008)
J Psychopharmacol 22, 162-171
   Abstract »    PDF »
Protection against beta-Amyloid-induced Apoptosis by Peptides Interacting with beta-Amyloid.
T. J. Nelson and D. L. Alkon (2007)
J. Biol. Chem. 282, 31238-31249
   Abstract »    Full Text »    PDF »
An internally controlled peripheral biomarker for Alzheimer's disease: Erk1 and Erk2 responses to the inflammatory signal bradykinin.
T. K. Khan and D. L. Alkon (2006)
PNAS 103, 13203-13207
   Abstract »    Full Text »    PDF »
Amyloid ion channels: A common structural link for protein-misfolding disease.
A. Quist, I. Doudevski, H. Lin, R. Azimova, D. Ng, B. Frangione, B. Kagan, J. Ghiso, and R. Lal (2005)
PNAS 102, 10427-10432
   Abstract »    Full Text »    PDF »
Oxidation of Cholesterol by Amyloid Precursor Protein and {beta}-Amyloid Peptide.
T. J. Nelson and D. L. Alkon (2005)
J. Biol. Chem. 280, 7377-7387
   Abstract »    Full Text »    PDF »
Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice.
R. Etcheberrigaray, M. Tan, I. Dewachter, C. Kuiperi, I. Van der Auwera, S. Wera, L. Qiao, B. Bank, T. J. Nelson, A. P. Kozikowski, et al. (2004)
PNAS 101, 11141-11146
   Abstract »    Full Text »    PDF »
Impairment of Hippocampal CA1 Heterosynaptic Transformation and Spatial Memory by beta -Amyloid25-35.
M.-K. Sun and D. L. Alkon (2002)
J Neurophysiol 87, 2441-2449
   Abstract »    Full Text »    PDF »
Amyloid {beta} protein forms ion channels: implications for Alzheimer's disease pathophysiology.
H. LIN, R. BHATIA, and R. LAL (2001)
FASEB J 15, 2433-2444
   Abstract »    Full Text »    PDF »
Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities.
C.-C. Shieh, M. Coghlan, J. P. Sullivan, and M. Gopalakrishnan (2000)
Pharmacol. Rev. 52, 557-594
   Abstract »    Full Text »    PDF »
Fresh and globular amyloid {beta} protein (1-42) induces rapid cellular degeneration: evidence for A{beta}P channel-mediated cellular toxicity.
R. BHATIA, H. LIN, and R. LAL (2000)
FASEB J 14, 1233-1243
   Abstract »    Full Text »
Fresh and nonfibrillar amyloid {beta} protein(1-40) induces rapid cellular degeneration in aged human fibroblasts: evidence for A{beta}P-channel-mediated cellular toxicity.
Y. J. ZHU, H. LIN, and R. LAL (2000)
FASEB J 14, 1244-1254
   Abstract »    Full Text »
The HHQK Domain of beta -Amyloid Provides a Structural Basis for the Immunopathology of Alzheimer's Disease.
D. Giulian, L. J. Haverkamp, J. Yu, W. Karshin, D. Tom, J. Li, A. Kazanskaia, J. Kirkpatrick, and A. E. Roher (1998)
J. Biol. Chem. 273, 29719-29726
   Abstract »    Full Text »    PDF »
Amyloid beta  Protein-(1-42) Forms Calcium-permeable, Zn2+-sensitive Channel.
S. K. Rhee, A. P. Quist, and R. Lal (1998)
J. Biol. Chem. 273, 13379-13382
   Abstract »    Full Text »    PDF »
Alzheimer's-specific effects of soluble beta -amyloid on protein kinase C-alpha and -gamma degradation in human fibroblasts.
A. Favit, M. Grimaldi, T. J. Nelson, and D. L. Alkon (1998)
PNAS 95, 5562-5567
   Abstract »    Full Text »    PDF »
Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease.
L. Gasparini, M. Racchi, G. Binetti, M. Trabucchi, S. B. Solerte, D. Alkon, R. Etcheberrigaray, G. Gibson, J. Blass, R. Paoletti, et al. (1998)
FASEB J 12, 17-34
   Abstract »    Full Text »
Secondary Structure and Ca2+-induced Conformational Change of Calexcitin, a Learning-associated Protein.
G. A. Ascoli, K. X. Luu, J. L. Olds, T. J. Nelson, P. A. Gusev, C. Bertucci, E. Bramanti, A. Raffaelli, P. Salvadori, and D. L. Alkon (1997)
J. Biol. Chem. 272, 24771-24779
   Abstract »    Full Text »    PDF »
Impaired Calcium Regulation in Subcortical Vascular Encephalopathy.
A. Eckert, M. Oster, H. Forstl, M. Hennerici, and W. E. Muller (1997)
Stroke 28, 1351-1356
   Abstract »    Full Text »
Calexcitin: A signaling protein that binds calcium and GTP, inhibits potassium channels, and enhances membrane excitability.
T. J. Nelson, S. Cavallaro, C.-L. Yi, D. McPhie, B. G. Schreurs, P. A. Gusev, A. Favit, O. Zohar, J. Kim, S. Beushausen, et al. (1996)
PNAS 93, 13808-13813
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)