کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3070006 1580710 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease
چکیده انگلیسی

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 KV1.3 channels in T lymphocytes of AD patients. Although intrinsic KV1.3 properties in patients were similar to healthy individuals, glutamate (1–1000 μM) failed to yield the hyperpolarizing shift normally observed in KV1.3 steady-state inactivation (− 4.4 ± 2.7 mV in AD vs. − 14.3 ± 2.5 mV in controls, 10 μM 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 KV1.3 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 37, Issue 2, February 2010, Pages 339–348
نویسندگان
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