Etcheberrigaray R, Ito E, Oka K, Tofel-Grehl B, Gibson G E, Alkon D L
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8209-13. doi: 10.1073/pnas.90.17.8209.
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.
由于记忆丧失是阿尔茨海默病（AD）的特征，并且由于在软体动物和哺乳动物的记忆形成过程中钾离子通道都会发生变化，因此我们研究了钾离子通道功能，将其作为AD病理学的一个可能位点，进而也作为一种可能的诊断指标。AD成纤维细胞中始终不存在一种对四乙铵（TEA）敏感的113皮安（pS）钾离子通道，而在年轻和老年对照成纤维细胞中该通道则经常存在。第二（166 pS）种钾离子通道在所有三组细胞中均有存在。在所有情况下，细胞外钾离子浓度升高都会使细胞内钙离子浓度升高。TEA使年轻和老年对照成纤维细胞发生去极化并导致细胞内钙离子浓度升高，但对AD成纤维细胞却没有这种作用。113 pS TEA敏感钾离子通道始终缺失以及TEA诱导的钙离子信号表明AD成纤维细胞中存在钾离子通道功能障碍。这些结果提示存在一种实验室方法的可能性，该方法能够在诊断上区分有或没有AD家族史的AD患者与年龄匹配的正常对照，以及与患有非AD神经和精神疾病的患者。
