CAMP-dependent kinase (PKA) phosphorylates the L-type calcium channel (LTCC) at a single serine residue in the C-terminus of the alpha1 subunit and in doing so increases the number of channels that will be activated by depolarization. In muscle PKA action on the LTCC is dependent upon its binding to A kinase anchoring proteins (AKAPs). In neurons LTCCs localize to similar subcellular locations as AKAP79, an AKAP that not only targets PKA to its substrates, but also the phosphatase calcineurin (CaN). The goal of the proposed research is to determine whether PKA and CaN together influence the activity of the LTCC in a manner that requires AKAP79 anchoring. I will disrupt AKAP79 anchoring of PKA and CaN and study how this affects the ability of these enzymes to regulate the channel by measuring changes in LTCC peak current using whole cell electrophysiology. Secondly, I will measure the rates of changes in intermolecular proximity between members of the channel-AKAP-PKA/-CaN complex using fluorescence resonance energy transfer and correlate these changes with LTCC regulation by simultaneously recording calcium channel currents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS051963-03
Application #
7230549
Study Section
Special Emphasis Panel (ZNS1-SRB-M (13))
Program Officer
Silberberg, Shai D
Project Start
2005-03-01
Project End
2008-02-29
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
3
Fiscal Year
2007
Total Cost
$26,912
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Oliveria, Seth F; Dittmer, Philip J; Youn, Dong-ho et al. (2012) Localized calcineurin confers Ca2+-dependent inactivation on neuronal L-type Ca2+ channels. J Neurosci 32:15328-37
Oliveria, Seth F; Dell'Acqua, Mark L; Sather, William A (2007) AKAP79/150 anchoring of calcineurin controls neuronal L-type Ca2+ channel activity and nuclear signaling. Neuron 55:261-75