Our long-term goals are to understand the function and biology of ionic channels of excitable cell membranes in molecular terms. How do they open and close, how do they recognize permeant ions, what is their 3-dimensional structure, and what are their origins? The major specific aims during this grant period are: 1) To identify specific chemical groups and drug binding sites on Na channels that influence activation or inactivation of the channels. We will study reagents reaction with amino, sulfhydryl, and carboxyl groups and characterize the effects of the veratridine-class of lipid-soluble gating modifiers. 2) To characterize selectivity, gating, and drug modifiability of two less well-understood potassium channels, the inward rectifier and the A current channel. The motivation is to see if evidence for possible evolutionary relatedness between these channels and the delayed rectifier K channel can be found. 3) To understand the ionic selectivity of anion channels, both of the transmitter-activated and transmitter-insensitive type. Better inhibitors for anion channels will be sought. The experiments will use macroscopic voltage clamp and patch clamp on a variety of invertebrate and vertebrate excitable cell, both from the adult and in culture. The research will reveal fundamental properties of these membrane proteins that are central in cellular excitability, volume regulation, and pH regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS008174-22
Application #
3393727
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1974-10-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
22
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Jung, Seung-Ryoung; Deng, Yi; Kushmerick, Christopher et al. (2018) Minimizing ATP depletion by oxygen scavengers for single-molecule fluorescence imaging in live cells. Proc Natl Acad Sci U S A 115:E5706-E5715
Yu, Haijie; Seo, Jong Bae; Jung, Seung-Ryoung et al. (2015) Noradrenaline upregulates T-type calcium channels in rat pinealocytes. J Physiol 593:887-904
Hille, Bertil; Dickson, Eamonn J; Kruse, Martin et al. (2015) Phosphoinositides regulate ion channels. Biochim Biophys Acta 1851:844-56
Hille, Bertil; Dickson, Eamonn; Kruse, Martin et al. (2014) Dynamic metabolic control of an ion channel. Prog Mol Biol Transl Sci 123:219-47
Yoon, Jin-Young; Jung, Seung-Ryoung; Hille, Bertil et al. (2014) Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes. Am J Physiol Cell Physiol 306:C726-35
Dickson, Eamonn J; Falkenburger, Björn H; Hille, Bertil (2013) Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling. J Gen Physiol 141:521-35
Falkenburger, Björn H; Dickson, Eamonn J; Hille, Bertil (2013) Quantitative properties and receptor reserve of the DAG and PKC branch of G(q)-coupled receptor signaling. J Gen Physiol 141:537-55
Kim, Mean-Hwan; Seo, Jong Bae; Burnett, Lindsey A et al. (2013) Characterization of store-operated Ca2+ channels in pancreatic duct epithelia. Cell Calcium 54:266-75
Kruse, Martin; Hille, Bertil (2013) The phosphoinositide sensitivity of the K(v) channel family. Channels (Austin) 7:530-6
Dickson, Eamonn J; Duman, Joseph G; Moody, Mark W et al. (2012) Orai-STIM-mediated Ca2+ release from secretory granules revealed by a targeted Ca2+ and pH probe. Proc Natl Acad Sci U S A 109:E3539-48

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