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Neurobiol Dis. 2010 Feb;37(2):339-48. doi: 10.1016/j.nbd.2009.10.012. Epub 2009 Oct 20.

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

Author information

1
Department of Neurology, Laboratory of Experimental Neurophysiology, Medical School, University of Athens, Eginition Hospital, Athens, Greece. cpoulop@med.uoa.gr

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.

PMID:
19850126
DOI:
10.1016/j.nbd.2009.10.012
[Indexed for MEDLINE]

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