In:
Annals of the New York Academy of Sciences, Wiley, Vol. 1097, No. 1 ( 2007-02), p. 265-277
Abstract:
Abstract: Intracellular Ca 2+ signaling involves Ca 2+ liberation through both inositol triphosphate and ryanodine receptors (IP 3 R and RyR). However, little is known of the functional interactions between these Ca 2+ sources in either neuronal physiology, or during Ca 2+ disruptions associated with Alzheimer's disease (AD). By the use of whole‐cell recordings and 2‐photon Ca 2+ imaging in cortical slices we distinguished between IP 3 R‐ and RyR‐mediated Ca 2+ components in nontransgenic (non‐Tg) and AD mouse models and demonstrate powerful signaling interactions between these channels. Ca 2+ ‐induced Ca 2+ release (CICR) through RyR contributed modestly to Ca 2+ signals evoked by photoreleased IP 3 in cortical neurons from non‐Tg mice. In contrast, the exaggerated signals in 3×Tg‐AD and PS1 KI mice resulted primarily from enhanced CICR through RyR, rather than through IP 3 R, and were associated with increased RyR expression levels. Moreover, membrane hyperpolarizations evoked by IP 3 in neurons from AD mouse models were even greater than expected simply from the exaggerated Ca 2+ signals, pointing to an increased coupling efficiency between cytosolic [Ca 2+ ] and K + channel regulation. Our results highlight the critical roles of RyR‐mediated Ca 2+ signaling in both neuronal physiology and pathophysiology, and point to presenilin ‐linked disruptions in RyR signaling as an important genetic factor in AD.
Type of Medium:
Online Resource
ISSN:
0077-8923
,
1749-6632
DOI:
10.1196/annals.1379.025
Language:
English
Publisher:
Wiley
Publication Date:
2007
detail.hit.zdb_id:
2834079-6
detail.hit.zdb_id:
211003-9
detail.hit.zdb_id:
2071584-5
SSG:
11
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