Work in our lab is aimed at elucidating the molecular structure and function of potassium (K+) channel genes as well as attempting to understand the role(s) these genes might play in mammalian behavior. Here we propose to study voltage-gated K+ channel genes in the central nervous system (CNS) and auditory system of normal, mutant and transgenic mice. During the previous funding period, we cloned and mapped 6 different murine voltage-gated K+ channel genes to their chromosomal locations and found that the expression of one of these, MK1, is reduced approximately 50% in brains and cochlea of a deaf mutant mouse, deafwaddler. Here we propose to extend these findings by determining the cellular and subcellular distribution of these K+ channels in both the central nervous system and in the cochlea of normal and deaf mice. We will also explore the regulation of these genes and construct transgenic mice that express normal and mutant K+ channels. These studies will provide molecular insights into the distribution, gene expression and function of K+ channels in the mammalian brain and auditory system. The studies on dfw mutant animals provide the exciting possibility of linking K+ channel function with a neurological phenotype.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027206-05
Application #
2266315
Study Section
Neurology C Study Section (NEUC)
Project Start
1989-04-01
Project End
1996-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Grigg, J J; Brew, H M; Tempel, B L (2000) Differential expression of voltage-gated potassium channel genes in auditory nuclei of the mouse brainstem. Hear Res 140:77-90
Hallows, J L; Tempel, B L (1998) Expression of Kv1.1, a Shaker-like potassium channel, is temporally regulated in embryonic neurons and glia. J Neurosci 18:5682-91
Allen, M L; Koh, D S; Tempel, B L (1998) Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing Kv1.1 mRNA. Proc Natl Acad Sci U S A 95:7693-8
Street, V A; Tempel, B L (1997) Physical mapping of potassium channel gene clusters on mouse chromosomes three and six. Genomics 44:110-7
Smart, S L; Bosma, M M; Tempel, B L (1997) Identification of the delayed rectifier potassium channel, Kv1.6, in cultured astrocytes. Glia 20:127-34
Street, V A; Hopkins, W F; Tempel, B L (1996) Genomic structure, sequence, and physiological expression of mKv 1.5, a mouse potassium channel gene. Epilepsy Res Suppl 12:165-75
Street, V A; Robinson, L C; Erford, S K et al. (1995) Molecular genetic analysis of distal mouse chromosome 6 defines gene order and positions of the deafwaddler and opisthotonos mutations. Genomics 29:123-30
Lock, L F; Gilbert, D J; Street, V A et al. (1994) Voltage-gated potassium channel genes are clustered in paralogous regions of the mouse genome. Genomics 20:354-62
Wang, H; Kunkel, D D; Schwartzkroin, P A et al. (1994) Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain. J Neurosci 14:4588-99
Hopkins, W F; Demas, V; Tempel, B L (1994) Both N- and C-terminal regions contribute to the assembly and functional expression of homo- and heteromultimeric voltage-gated K+ channels. J Neurosci 14:1385-93

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