Surface L-type Ca2+ channel expression levels are increased in aged hippocampus

Félix Luis Núñez-Santana, M Matthew Oh, Marcia Diana Antion, Amy Lee, Johannes Wilhelm Hell, John F Disterhoft*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Age-related increase in L-type Ca2+ channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca2+ influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav1.2 and Cav1.3 subunits of LTCCs, we systematically re-examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Cav1.2 and Cav1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Cav1.2 in the CA1 and CA3 regions and of Cav1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Cav1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Cav1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age-related cognitive deficits cannot be attributed to a global change in L-type channel expression nor to the level of phosphorylation of Cav1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age-related increase in L-type Ca2+ channel activity in CA1 pyramidal neurons.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalAging Cell
Volume13
Issue number1
DOIs
StatePublished - Feb 1 2014

Fingerprint

Pyramidal Cells
Hippocampus
Cell Membrane
Biotinylation
Hippocampal CA3 Region
Neurons
Dentate Gyrus
Western Blotting
Phosphorylation
Antibodies
Proteins

Keywords

  • Biotinylation
  • Ca1.2
  • Ca1.3
  • Calcium
  • Phosphorylation
  • qRT-PCR

ASJC Scopus subject areas

  • Cell Biology
  • Aging
  • Medicine(all)

Cite this

Núñez-Santana, Félix Luis ; Oh, M Matthew ; Antion, Marcia Diana ; Lee, Amy ; Hell, Johannes Wilhelm ; Disterhoft, John F. / Surface L-type Ca2+ channel expression levels are increased in aged hippocampus. In: Aging Cell. 2014 ; Vol. 13, No. 1. pp. 111-120.
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Surface L-type Ca2+ channel expression levels are increased in aged hippocampus. / Núñez-Santana, Félix Luis; Oh, M Matthew; Antion, Marcia Diana; Lee, Amy; Hell, Johannes Wilhelm; Disterhoft, John F.

In: Aging Cell, Vol. 13, No. 1, 01.02.2014, p. 111-120.

Research output: Contribution to journalArticle

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AU - Núñez-Santana, Félix Luis

AU - Oh, M Matthew

AU - Antion, Marcia Diana

AU - Lee, Amy

AU - Hell, Johannes Wilhelm

AU - Disterhoft, John F

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