Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease

René Etcheberrigaray, Etsuro Ito, Kotaro Oka, Beth Tofel-Grehl, Gary E. Gibson, Daniel L. Alkon

研究成果: Article

121 引用 (Scopus)

抄録

Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders.

元の言語English
ページ(範囲)8209-8213
ページ数5
ジャーナルProceedings of the National Academy of Sciences of the United States of America
90
発行部数17
出版物ステータスPublished - 1993 9 1
外部発表Yes

Fingerprint

Potassium Channels
Alzheimer Disease
Fibroblasts
Tetraethylammonium
Mollusca
Memory Disorders
Nervous System Diseases
Psychiatry
Mammals
Potassium
Pathology

ASJC Scopus subject areas

  • General
  • Genetics

これを引用

Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. / Etcheberrigaray, René; Ito, Etsuro; Oka, Kotaro; Tofel-Grehl, Beth; Gibson, Gary E.; Alkon, Daniel L.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 90, 番号 17, 01.09.1993, p. 8209-8213.

研究成果: Article

Etcheberrigaray, René ; Ito, Etsuro ; Oka, Kotaro ; Tofel-Grehl, Beth ; Gibson, Gary E. ; Alkon, Daniel L. / Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. :: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 巻 90, 番号 17. pp. 8209-8213.
@article{7c671b99ff724274b65c80845873b841,
title = "Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease",
abstract = "Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders.",
author = "Ren{\'e} Etcheberrigaray and Etsuro Ito and Kotaro Oka and Beth Tofel-Grehl and Gibson, {Gary E.} and Alkon, {Daniel L.}",
year = "1993",
month = "9",
day = "1",
language = "English",
volume = "90",
pages = "8209--8213",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "17",

}

TY - JOUR

T1 - Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease

AU - Etcheberrigaray, René

AU - Ito, Etsuro

AU - Oka, Kotaro

AU - Tofel-Grehl, Beth

AU - Gibson, Gary E.

AU - Alkon, Daniel L.

PY - 1993/9/1

Y1 - 1993/9/1

N2 - Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders.

AB - Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders.

UR - http://www.scopus.com/inward/record.url?scp=0027220966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027220966&partnerID=8YFLogxK

M3 - Article

C2 - 8367484

AN - SCOPUS:0027220966

VL - 90

SP - 8209

EP - 8213

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

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

SN - 0027-8424

IS - 17

ER -