Ion channel modulation is a fundamental feature of dynamic electrical signalling in the brain. Voltage-dependent K channels are intimately involved in regulating neuronal activity and may be potential targets for therapeutic drugs.
The specific aim of this research proposal is to study the functional consequences and structural correlates of tyrosine phosphorylation of ion channels using the cloned voltage-gated potassium channel, Kv1.3, in a heterologous expression system. Preliminary data indicate that the activity of Kv1.3, expressed in HEK 293 cells, can be modulated by co-expression of the cellular tyrosine kinase v-src or treatment with the tyrosine phosphatase inhibitor pervanadate. Biochemical data from others in the Levitan laboratory have shown that both of these treatments increase the tyrosine phosphorylation of Kv1.3. Site-directed mutagenesis and electrophysiological recordings in cDNA transfected cell lines will be combined to (1) elucidate the biophysical properties of Kv1.3 that are modulated by tyrosine phosphorylation, and (2) identify the tyrosine residue(s) whose phosphorylation is responsible for the modulation. This combined biophysical/molecular approach will provide fundamental information about the molecular details and cellular consequences of ion channel modulation in neurons and other cell types.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS009952-01
Application #
2261977
Study Section
Special Emphasis Panel (ZRG1-NLS-3 (01))
Project Start
1995-12-01
Project End
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Organized Research Units
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454