G-protein coupled inwardly rectifying potassium channel (GIRK) regulates neuronal excitability by mediating postsynaptic inhibitory effects of various transmitter in brain. Recent studies showing the presence of GIRK in dendritic spines suggest that excitatory neurotransmitter receptors may regulate GIRK function. Indeed, neuronal activity increased GIRK surface expression in dendrites and spines of hippocampal neurons in a protein synthesis and a protein phosphatase (PPI)-dependent manner. The objectives of this proposal are to investigate the molecular mechanisms and physiological consequence of activity-induced GIRK surface expression. Live-imaging and surface immunostaining will be performed to investigate how protein synthesis, post translational surface trafficking of GIRK and PP1 activity contribute to activity-induced GIRK surface expression (Specific Aim A-C). To study the functional significance of activity-induced GIRK surface expression (Specific Aim D), whole-cell patch clamp recording of GABAb-mediated GIRK current before and after neuronal activity will be performed. These studies will reveal novel mechanisms for modulating inhibitory synaptic function ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH073187-03
Application #
7158559
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Curvey, Mary F
Project Start
2004-12-01
Project End
2007-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
3
Fiscal Year
2007
Total Cost
$52,048
Indirect Cost
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143