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

Aging Cell

Félix Luis Núñez-Santana³  Myongsoo Matthew Oh³  Marcia Diana Antion³  Amy Lee¹  Johannes Wilhelm Hell² 

[1] Departments of Molecular Physiology and Biophysics, Otolaryngology-Head and Neck Surgery, and Neurology, University of Iowa, Iowa City, IA, USA;Department of Pharmacology, University of California, Davis, CA, USA;Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

关键词: biotinylation;    Cav1.2;    Cav1.3;    calcium;    phosphorylation;    qRT‐PCR;   

DOI  :  10.1111/acel.12157

来源: Wiley

【 摘 要 】

Summary

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 Ca_v1.2 and Ca_v1.3 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 Ca_v1.2 and Ca_v1.3 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 Ca_v1.2 in the CA1 and CA3 regions and of Ca_v1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Ca_v1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Ca_v1.2 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 Ca_v1.2 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.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.