Department of Neurology, Laboratory of Experimental Neurophysiology, Medical School, University of Athens, Eginition Hospital, Athens, Greece.
Neurobiol Dis. 2010 Feb;37(2):339-48. doi: 10.1016/j.nbd.2009.10.012. Epub 2009 Oct 20.
In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.
在阿尔茨海默病（AD）中，已经在神经和外周组织中报告了钾通道异常。在此，我们使用全细胞膜片钳技术，证明了 AD 患者 T 淋巴细胞中谷氨酸依赖性的 K(V)1.3 通道异常调节。尽管患者的内在 K(V)1.3 特性与健康个体相似，但谷氨酸（1-1000 microM）未能产生 K(V)1.3 稳态失活中通常观察到的超极化偏移（AD 中为-4.4+/-2.7 mV，对照组为-14.3+/-2.5 mV，10 microM 谷氨酸），导致静息通道活性增加 4 倍。特异性激动剂和拮抗剂数据表明，这种异常是由于同源的 II 组 mGluRs 功能障碍所致。鉴于谷氨酸存在于血浆中，并且 mGluRs 和 K(V)1.3 通道都调节 T 淋巴细胞的反应性，我们的发现可能解释了 AD 中存在的免疫相关改变。此外，如果这种异常反映了神经组织中的相应变化，它可能为 AD 发病机制提供一个潜在的靶点。
