Increased phosphorylation of the neuronal L-type Ca2+ channel Cav1.2 during aging

Monika A. Davare, Johannes W Hell

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

An increase in Ca2+ influx through L-type Ca2+ channels is thought to contribute to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease. The molecular basis of the age-dependent up-regulation in neuronal L-type Ca2+ channel activity is largely unknown. We show that phosphorylation of the L-type channel Cav1.2 by cAMP-dependent protein kinase is increased >2-fold in the hippocampus of aged rats. The hippocampus is critical for learning and is one of the first brain regions to be affected in Alzheimer's disease. Phosphorylation of Ca v1.2 by cAMP-dependent protein kinase strongly enhances its activity. Therefore, increased Cav1.2 phosphorylation may account for a substantial portion of the age-related rise in neuronal Ca2+ influx and its neuropathological consequences.

Original languageEnglish (US)
Pages (from-to)16018-16023
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number26
DOIs
StatePublished - Dec 23 2003
Externally publishedYes

Fingerprint

Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Hippocampus
Alzheimer Disease
Up-Regulation
Learning
Brain

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Increased phosphorylation of the neuronal L-type Ca2+ channel Cav1.2 during aging. / Davare, Monika A.; Hell, Johannes W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 26, 23.12.2003, p. 16018-16023.

Research output: Contribution to journalArticle

@article{cbd26782180a4f55a6bcb924b6e644d8,
title = "Increased phosphorylation of the neuronal L-type Ca2+ channel Cav1.2 during aging",
abstract = "An increase in Ca2+ influx through L-type Ca2+ channels is thought to contribute to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease. The molecular basis of the age-dependent up-regulation in neuronal L-type Ca2+ channel activity is largely unknown. We show that phosphorylation of the L-type channel Cav1.2 by cAMP-dependent protein kinase is increased >2-fold in the hippocampus of aged rats. The hippocampus is critical for learning and is one of the first brain regions to be affected in Alzheimer's disease. Phosphorylation of Ca v1.2 by cAMP-dependent protein kinase strongly enhances its activity. Therefore, increased Cav1.2 phosphorylation may account for a substantial portion of the age-related rise in neuronal Ca2+ influx and its neuropathological consequences.",
author = "Davare, {Monika A.} and Hell, {Johannes W}",
year = "2003",
month = "12",
day = "23",
doi = "10.1073/pnas.2236970100",
language = "English (US)",
volume = "100",
pages = "16018--16023",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "26",

}

TY - JOUR

T1 - Increased phosphorylation of the neuronal L-type Ca2+ channel Cav1.2 during aging

AU - Davare, Monika A.

AU - Hell, Johannes W

PY - 2003/12/23

Y1 - 2003/12/23

N2 - An increase in Ca2+ influx through L-type Ca2+ channels is thought to contribute to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease. The molecular basis of the age-dependent up-regulation in neuronal L-type Ca2+ channel activity is largely unknown. We show that phosphorylation of the L-type channel Cav1.2 by cAMP-dependent protein kinase is increased >2-fold in the hippocampus of aged rats. The hippocampus is critical for learning and is one of the first brain regions to be affected in Alzheimer's disease. Phosphorylation of Ca v1.2 by cAMP-dependent protein kinase strongly enhances its activity. Therefore, increased Cav1.2 phosphorylation may account for a substantial portion of the age-related rise in neuronal Ca2+ influx and its neuropathological consequences.

AB - An increase in Ca2+ influx through L-type Ca2+ channels is thought to contribute to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease. The molecular basis of the age-dependent up-regulation in neuronal L-type Ca2+ channel activity is largely unknown. We show that phosphorylation of the L-type channel Cav1.2 by cAMP-dependent protein kinase is increased >2-fold in the hippocampus of aged rats. The hippocampus is critical for learning and is one of the first brain regions to be affected in Alzheimer's disease. Phosphorylation of Ca v1.2 by cAMP-dependent protein kinase strongly enhances its activity. Therefore, increased Cav1.2 phosphorylation may account for a substantial portion of the age-related rise in neuronal Ca2+ influx and its neuropathological consequences.

UR - http://www.scopus.com/inward/record.url?scp=0346734114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346734114&partnerID=8YFLogxK

U2 - 10.1073/pnas.2236970100

DO - 10.1073/pnas.2236970100

M3 - Article

C2 - 14665691

AN - SCOPUS:0346734114

VL - 100

SP - 16018

EP - 16023

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 26

ER -