Redox sensitive calcium stores underlie enhanced after hyperpolarization of aged neurons: role for ryanodine receptor mediated calcium signaling.
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.
Bodhinathan
Karthik
K
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA.
Kumar
Ashok
A
Foster
Thomas C
TC
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004229:Dithiothreitol / Q000494:pharmacology; D004594:Electrophysiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium; D004229:Dithiothreitol