Abstract

The long-term goal of the project is to determine how therapeutic drugs and toxins affect neuronal ion channels.
The specific aims for the next 5 years of proposed funding concentrate on a pharmacological comparison of two sodium channel types in dorsal root ganglion (DRG) neurons: tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) channels. This focus was suggested in the review of the previous version of this application. Although TTX-S and TTX-R channels are also present in brain neurons, DRG cells were chosen as a model, since the proportion of TTX-R channels is generally small in brain, and the principal investigator already has substantial data on these channels in DRG. Whole-cell and single-channel patch clamp techniques will be used.
Five specific aims are proposed, comparing the effects on TTX-S and TTX-R channels of divalent cations, natural toxins, therapeutic drugs, protein phosphorylation, and G proteins. In addition to providing basic information, the results are expected to contribute to development of new therapeutic drugs and to understanding of brain function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS014144-21
Application #
2735533
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Liu, Yuan
Project Start
1979-05-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
21
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611

  Publications

Mori, T; Zhao, X; Zuo, Y et al. (2001) Modulation of neuronal nicotinic acetylcholine receptors by halothane in rat cortical neurons. Mol Pharmacol 59:732-43
Zhao, X; Yeh, J Z; Narahashi, T (2001) Post-stroke dementia. Nootropic drug modulation of neuronal nicotinic acetylcholine receptors. Ann N Y Acad Sci 939:179-86
Narahashi, T (2000) Neuroreceptors and ion channels as the basis for drug action: past, present, and future. J Pharmacol Exp Ther 294:26-Jan
Narahashi, T; Aistrup, G L; Marszalec, W et al. (1999) Neuronal nicotinic acetylcholine receptors: a new target site of ethanol. Neurochem Int 35:131-41
Aistrup, G L; Marszalec, W; Narahashi, T (1999) Ethanol modulation of nicotinic acetylcholine receptor currents in cultured cortical neurons. Mol Pharmacol 55:39-49
Uenishi, H; Huang, C S; Song, J H et al. (1999) Ion channel modulation as the basis for neuroprotective action of MS-153. Ann N Y Acad Sci 890:385-99
Oyaizu, M; Narahashi, T (1999) Modulation of the neuronal nicotinic acetylcholine receptor-channel by the nootropic drug nefiracetam. Brain Res 822:72-9
Narahashi, T; Aistrup, G L; Lindstrom, J M et al. (1998) Ion channel modulation as the basis for general anesthesia. Toxicol Lett 100-101:185-91
Narahashi, T; Huang, C S; Song, J H et al. (1997) Ion channels as targets for neuroprotective agents. Ann N Y Acad Sci 825:380-8
Huang, C S; Song, J H; Nagata, K et al. (1997) Effects of the neuroprotective agent riluzole on the high voltage-activated calcium channels of rat dorsal root ganglion neurons. J Pharmacol Exp Ther 282:1280-90

Showing the most recent 10 out of 65 publications