Enhanced ryanodine-mediated calcium release in mutant PS1-expressing Alzheimer's mouse models

Grace E. Stutzmann, Ian Smith, Antonella Caccamo, Salvatore Oddo, Ian Parker, Frank Laferla

Research output: Chapter in Book/Report/Conference proceedingConference contribution

87 Scopus citations

Abstract

Intracellular Ca2+ signaling involves Ca2+ liberation through both inositol triphosphate and ryanodine receptors (IP3R and RyR). However, little is known of the functional interactions between these Ca2+ sources in either neuronal physiology, or during Ca2+ disruptions associated with Alzheimer's disease (AD). By the use of whole-cell recordings and 2-photon Ca2+ imaging in cortical sliceswe distinguished between IP3R- and RyR-mediated Ca2+ components in nontransgenic (non-Tg) and AD mouse models and demonstrate powerful signaling interactions between these channels. Ca2+-induced Ca2+ release (CICR) through RyR contributed modestly to Ca 2+ signals evoked by photoreleased IP3 in cortical neurons from non-Tg mice. In contrast, the exaggerated signals in 3xTg-AD and PS1 KI mice resulted primarily from enhanced CICR through RyR, rather than through IP3R, and were associated with increased RyR expression levels. Moreover, membrane hyperpolarizations evoked by IP3 in neurons from AD mouse models were even greater than expected simply from the exaggerated Ca2+ signals, pointing to an increased coupling efficiency between cytosolic [Ca2+] 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.

Original languageEnglish (US)
Title of host publicationImaging and the Aging Brain
PublisherBlackwell Publishing Inc.
Pages265-277
Number of pages13
ISBN (Print)1573316598, 9781573316590
DOIs
StatePublished - Feb 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1097
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • 2-photon
  • 3xTg-AD
  • Alzheimer
  • Calcium
  • Cortex
  • Electrophysiology
  • Endoplasmic reticulum
  • IP3
  • Neuron
  • PS1
  • Ryanodine
  • Transgenic

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Stutzmann, G. E., Smith, I., Caccamo, A., Oddo, S., Parker, I., & Laferla, F. (2007). Enhanced ryanodine-mediated calcium release in mutant PS1-expressing Alzheimer's mouse models. In Imaging and the Aging Brain (pp. 265-277). (Annals of the New York Academy of Sciences; Vol. 1097). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1379.025