Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease

Autor: Cornelia Poulopoulou, Ioannis Markakis, Panagiota Davaki, Eleftheria Tsaltas, Antonis Rombos, Alexandros Hatzimanolis, Dimitrios Vassilopoulos
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Neurobiology of Disease, Vol 37, Iss 2, Pp 339-348 (2010)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2009.10.012
Popis: 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.
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