Article

Redox sensitive calcium stores underlie enhanced after hyperpolarization of aged neurons: role for ryanodine receptor mediated calcium signaling.

Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA.
Journal of Neurophysiology (impact factor: 3.32). 09/2010; 104(5):2586-93. DOI:10.1152/jn.00577.2010 pp.2586-93
Source: PubMed

ABSTRACT A decrease in the excitability of CA1 pyramidal neurons contributes to the age related decrease in hippocampal function and memory decline. Decreased neuronal excitability in aged neurons can be observed as an increase in the Ca(2+)- activated K(+)- mediated post burst afterhyperpolarization (AHP). In this study, we demonstrate that the slow component of AHP (sAHP) in aged CA1 neurons (aged-sAHP) is decreased ∼50% by application of the reducing agent dithiothreitol (DTT). The DTT-mediated decrease in the sAHP was age specific, such that it was observed in CA1 pyramidal neurons of aged (20-25 mo), but not young (6-9 mo) F344 rats. The effect of DTT on the aged-sAHP was blocked following depletion of intracellular Ca(2+) stores (ICS) by thapsigargin or blockade of ryanodine receptors (RyRs) by ryanodine, suggesting that the age-related increase in the sAHP was due to release of Ca(2+) from ICS through redox sensitive RyRs. The DTT-mediated decrease in the aged-sAHP was not blocked by inhibition of L-type voltage gated Ca(2+) channels (L-type VGCC), inhibition of Ser/Thr kinases, or inhibition of the large conductance BK potassium channels. The results add support to the idea that a shift in the intracellular redox state contributes to Ca(2+) dysregulation during aging.

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Keywords

age-related increase
 
aged-sAHP
 
CA1 neurons
 
CA1 pyramidal neurons
 
CA1 pyramidal neurons contributes
 
Decreased neuronal excitability
 
DTT-mediated decrease
 
hippocampal function
 
inhibition
 
L-type VGCC
 
L-type voltage gated Ca(2+)
 
large conductance BK potassium channels
 
memory decline
 
post burst afterhyperpolarization
 
redox sensitive RyRs
 
reducing agent dithiothreitol
 
ryanodine receptors
 
Ser/Thr kinases
 
slow component
 
thapsigargin