We are primarily interested in determining the mechanisms by which L-type calcium channels, and not other calcium entry routes, influence neuronal plasticity via changes in gene expression and protein synthesis. Specifically, we believe different alpha1 subunits of L-type calcium channels are uniquely responsible for activation of the transcription factors CREB and NFATc4, both of which regulate cellular excitability. The experiments we will use to address this question are organized into three specific aims: 1) Determine the molecular components of (alpha1C that are necessary and sufficient for activation of CREB. 2) Establish whether it is the (alpha1C and/or alpha1D comprised L-type calcium channel that regulates NFATc4 activation. 3) Elucidate the mechanism by which L-type calcium channels regulate NFAT-dependent transcription. Our overall goal is to comprehend why the expression of many genes influencing cell excitability are tightly regulated by calcium entry specifically through L-type calcium channels. Thus, we will gain insight into the mechanisms surrounding a variety of cellular events, including those linked to development, learning and memory, hyperalgesia, drug addiction and aging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS046198-02
Application #
6743110
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Stewart, Randall R
Project Start
2003-04-21
Project End
2006-04-20
Budget Start
2004-04-21
Budget End
2005-04-20
Support Year
2
Fiscal Year
2004
Total Cost
$31,612
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455