Surface L-type Ca2+ channel expression levels are increased in aged hippocampus
Article first published online: 1 OCT 2013
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 1, pages 111–120, February 2014
How to Cite
Núñez-Santana, F. L., Oh, M. M., Antion, M. D., Lee, A., Hell, J. W. and Disterhoft, J. F. (2014), Surface L-type Ca2+ channel expression levels are increased in aged hippocampus. Aging Cell, 13: 111–120. doi: 10.1111/acel.12157
- Issue published online: 16 JAN 2014
- Article first published online: 1 OCT 2013
- Accepted manuscript online: 29 AUG 2013 02:40AM EST
- Manuscript Accepted: 12 AUG 2013
- National Institutes of Health Grants. Grant Numbers: AG008796, AG017139, AG017502, DC009433, HL087120
- Carver Research Program of Excellence Award
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.