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Increased intraneuronal resting [Ca 2+ ] in adult Alzheimer’s disease mice
Author(s) -
Lopez José R.,
Lyckman Alvin,
Oddo Salvatore,
LaFerla Frank M.,
Querfurth Henry W.,
Shtifman Alexander
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.05135.x
Subject(s) - ryanodine receptor , extracellular , neurodegeneration , chemistry , intracellular , homeostasis , inositol trisphosphate receptor , medicine , endocrinology , inositol trisphosphate , channel blocker , receptor , inositol , calcium , microbiology and biotechnology , biology , biochemistry , disease , organic chemistry
Abstract Neurodegeneration in Alzheimer’s disease (AD) has been linked to intracellular accumulation of misfolded proteins and dysregulation of intracellular Ca 2+ . In the current work, we determined the contribution of specific Ca 2+ pathways to an alteration in Ca 2+ homeostasis in primary cortical neurons from an adult triple transgenic (3xTg‐AD) mouse model of AD that exhibits intraneuronal accumulation of β‐amyloid proteins. Resting free Ca 2+ concentration ([Ca 2+ ] i ), as measured with Ca 2+ ‐selective microelectrodes, was greatly elevated in neurons from 3xTg‐AD and APP SWE mouse strains when compared with their respective non‐transgenic neurons, while there was no alteration in the resting membrane potential. In the absence of the extracellular Ca 2+ , the [Ca 2+ ] i returned to near normal levels in 3xTg‐AD neurons, demonstrating that extracellular Ca 2+ contributed to elevated [Ca 2+ ] i . Application of nifedipine, or a non‐L‐type channel blocker, SKF‐96365, partially reduced [Ca 2+ ] i . Blocking the ryanodine receptors, with ryanodine or FLA‐365 had no effect, suggesting that these channels do not contribute to the elevated [Ca 2+ ] i . Conversely, inhibition of inositol trisphosphate receptors with xestospongin C produced a partial reduction in [Ca 2+ ] i . These results demonstrate that an elevation in resting [Ca 2+ ] i , contributed by aberrant Ca 2+ entry and release pathways, should be considered a major component of the abnormal Ca 2+ homeostasis associated with AD.