1. Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.
- Author
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Poulopoulou C, Markakis I, Davaki P, Tsaltas E, Rombos A, Hatzimanolis A, and Vassilopoulos D
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease immunology, Alzheimer Disease physiopathology, Brain Infarction immunology, Brain Infarction metabolism, Brain Infarction physiopathology, Cell Membrane drug effects, Cell Membrane metabolism, Cell Proliferation drug effects, Cells, Cultured, Excitatory Amino Acid Agonists pharmacology, Excitatory Amino Acid Antagonists pharmacology, Female, Glutamic Acid pharmacology, Humans, Ion Channel Gating drug effects, Ion Channel Gating physiology, Kv1.3 Potassium Channel drug effects, Lymphocyte Activation drug effects, Lymphocyte Activation physiology, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Mitogens pharmacology, Neuroimmunomodulation physiology, Patch-Clamp Techniques, Phytohemagglutinins pharmacology, Receptors, Metabotropic Glutamate agonists, T-Lymphocytes drug effects, T-Lymphocytes immunology, Alzheimer Disease metabolism, Glutamic Acid metabolism, Kv1.3 Potassium Channel metabolism, Receptors, Metabotropic Glutamate metabolism, T-Lymphocytes metabolism
- Abstract
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.
- Published
- 2010
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