The GIRK family of potassium channels mediates important functions in both cardiac and neuronal cells. The channels are composed of subunits that assemble to form a tetratmeric channel; however, how the subunits assemble to form a functional channel is not well known. Studies have shown that subunit interaction promotes proper expression and formation of the channel. Because channels may have variable composition, knowledge of the interaction between subunits may provide additional clues to differential cell function. This proposal is aimed at understanding how subunits interact, and particularly, examining specific regions of the GIRK 1 subunit that affect channel formation and expression. Preliminary data obtained from deletion mutants of GIRK 1 in oocytes suggest that a region of the C-terminus is important for channel function. The applicant will further examine how the wild type subunits interact and how this specific region of the GIRK 1 subunit is involved in the formation of the channel. The last set of experiments will address the role of GIRK 1 in the trafficking of the channel. Knowledge of GIRK channel assembly may provide useful information related to the effects of differential channel expression in specific cell types.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS042481-02
Application #
6655663
Study Section
Special Emphasis Panel (ZRG1-MDCN-3 (01))
Program Officer
Stewart, Randall
Project Start
2001-09-30
Project End
Budget Start
2002-09-30
Budget End
2003-09-29
Support Year
2
Fiscal Year
2002
Total Cost
$45,068
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Sarac, Radmila; Hou, Ping; Hurley, Karen M et al. (2005) Mutation of critical GIRK subunit residues disrupts N- and C-termini association and channel function. J Neurosci 25:1836-46