β-Amyloid peptide blocks the response of α7-containing nicotinic receptors on hippocampal neurons

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 8 - Trang 4734-4739 - 2001
Qing-song Liu1, Hideki Kawai2,3,4, Darwin K. Berg2,3,4
1Neurobiology Section, Division of Biology, University of California at San Diego, La Jolla, CA 92093-0357, USA.
2Neurobiology Section, Division of Biology, 0357, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0357.
3Neurobiology Section, Division of Biology, University of California at San Diego, La Jolla, CA 92093-0357
4The Salk Institute for Biological Studies, La Jolla, CA, and

Tóm tắt

Alzheimer's disease produces a devastating decline in mental function, with profound effects on learning and memory. Early consequences of the disease include the specific loss of cholinergic neurons in brain, diminished cholinergic signaling, and the accumulation of β-amyloid peptide in neuritic plaques. Of the nicotinic acetylcholine receptors at risk, the most critical may be those containing the α7 gene product (α7-nAChRs), because they are widespread, have a high relative permeability to calcium, and regulate numerous cellular events in the nervous system. With the use of whole-cell patch–clamp recording we show here that nanomolar concentrations of β-amyloid peptides specifically and reversibly block α7-nAChRs on rat hippocampal neurons in culture. The block is noncompetitive, voltage-independent, and use-independent and is mediated through the N-terminal extracellular domain of the receptor. It does not appear to require either calcium influx or G protein activation. β-Amyloid blockade is likely to be a common feature of α7-nAChRs because it applies to the receptors at both somato-dendritic and presynaptic locations on rat hippocampal neurons and extends to homologous receptors on chick ciliary ganglion neurons as well. Because α7-nAChRs in the central nervous system are thought to have numerous functions and recently have been implicated in learning and memory, impaired receptor function in this case may contribute to cognitive deficits associated with Alzheimer's disease.

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Tài liệu tham khảo

10.1136/jnnp.66.2.137

10.1038/399a023

10.1016/S0896-6273(00)80115-4

10.1126/science.7058341

10.1016/0022-510X(82)90045-4

10.1111/j.1471-4159.1983.tb11311.x

10.1016/S0169-328X(99)00030-3

J O Rinne, T Myllykyla, P Lonnberg, P Marjamaki Brain Res 547, 167–170 (1999).

10.1016/S0169-328X(00)00031-0

10.1016/S0306-4522(00)00071-3

10.1146/annurev.ne.16.030193.002155

10.1146/annurev.ph.57.030195.002513

10.1073/pnas.90.15.6971

10.1523/JNEUROSCI.13-02-00596.1993

10.1126/science.7569895

10.1038/383713a0

10.1523/JNEUROSCI.15-05-03679.1995

10.1523/JNEUROSCI.14-02-00889.1994

10.1523/JNEUROSCI.18-23-09954.1998

10.1523/JNEUROSCI.18-17-06871.1998

10.1016/S0014-5793(97)00600-5

10.1016/S0896-6273(00)80253-6

10.1523/JNEUROSCI.17-19-07210.1997

10.1523/JNEUROSCI.19-10-03701.1999

10.1523/JNEUROSCI.18-20-08228.1998

10.1523/JNEUROSCI.19-07-02693.1999

S Hefft, S Hulo, D Bertrand, D Muller J Physiol (London) 510, 709–716 (1999).

10.1016/S0896-6273(00)80773-4

10.1016/S0896-6273(00)00042-8

10.1101/lm.5.4.302

10.1016/S0006-8993(97)00536-2

10.1016/S0306-4522(97)00224-8

10.1097/00008877-199911000-00014

10.1046/j.1460-9568.1999.00676.x

10.1074/jbc.275.8.5626

10.1046/j.1471-4159.2000.0751155.x

10.1016/S0166-2236(97)01144-2

10.1046/j.1471-4159.1998.70052179.x

10.1523/JNEUROSCI.06-10-03044.1986

10.1523/JNEUROSCI.19-23-10280.1999

10.1523/JNEUROSCI.20-11-04021.2000

10.1038/366479a0

10.1126/science.1718042

10.1002/(SICI)1097-4695(199712)33:7<968::AID-NEU8>3.0.CO;2-6

10.1016/0165-0270(91)90017-T

10.1007/BF00656997

10.1016/0896-6273(94)90161-9

10.1016/0896-6273(93)90118-B

10.1016/0301-0082(91)90019-W

M Alkondon, E X Albuquerque J Pharmacol Exp Ther 265, 1455–1473 (1993).

10.1523/JNEUROSCI.17-21-08201.1997

10.1523/JNEUROSCI.18-24-10335.1998

10.1111/j.1469-7793.1998.651bm.x

10.1523/JNEUROSCI.21-01-j0003.2001

10.1073/pnas.91.25.12243

10.1002/1531-8249(199904)45:4<504::AID-ANA12>3.0.CO;2-9

10.1074/jbc.270.13.7013

10.1023/A:1021691918517

10.1073/pnas.96.6.3228

10.1523/JNEUROSCI.20-11-04050.2000

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Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 8

4734-4739

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