Methods and compositions related to the identification of compounds that block neurotransmitter release are disclosed. Using the methods of the present invention, candidate compounds may be screened for the ability to bind to presynaptic calcium channels such that the docking of presynaptic vesicles to presynaptic calcium channels will be inhibited. The present invention also discloses peptides useful in the screening methods.
Methods Of Identifying Specific Inactivation Gate Inhibitors Of The Sodium Channel
William A. Catterall - Seattle WA Galen Eaholtz - Seattle WA
Assignee:
University of Washington - Seattle WA
International Classification:
G01N 3353
US Classification:
435 72
Abstract:
Assay for identifying an inactivation gate inhibitor of a sodium channel, by: establishing first and a second cultures of cells having a wild-type sodium channel and third and a fourth cultures of cells having a noninactivating mutant sodium channel; measuring a baseline sodium current for one or more cells in the first and the second cultures, and a baseline inactivation rate for one or more cells in the third and the fourth cultures; treating the cells in the first and the third cultures with either a candidate inhibitor or an IFM amide control, and the cells in the second and the fourth cultures with an inactive control peptide; measuring a test sodium current in one or more cells in the first and the second cultures, and a test inactivation rate in one or more cells in the third and the fourth cultures; and determining that the candidate inhibitor is an inactivation gate inhibitor of the sodium channel if the test sodium current of the cells in the first culture is lower than the baseline of the first culture, the test sodium current of the cells in the second culture is about equal to the baseline of the second culture, the test inactivation rate of the cells in the third culture is higher than the baseline of the third culture, the test inactivation rate of the cells in the fourth culture is about equal to the baseline of the fourth culture, and the candidate inhibitor restores sodium channel inactivation in cells of the third culture to an extent at least equal to the IFM amide control. The candidate inhibitor comprises: ##STR1## wherein R. sub. 1 is straight or branched chain alkyl having a neutral charge; R. sub.
Methods And Compositions For Screening For Presynaptic Calcium Channel Blockers
Methods and compositions related to the identification of compounds that block neurotransmitter release are disclosed. Using the methods of the present invention, candidate compounds may be screened for the ability to bind to presynaptic calcium channels such that the docking of presynaptic vesicles to presynaptic calcium channels will be inhibited. The present invention also discloses peptides useful in the screening methods.
Name / Title
Company / Classification
Phones & Addresses
William A. Catterall Phd
University of Washington Pharmacy Department
F431 Med BLDG 1959 PCF ST, Seattle, WA 98195 PO Box 357630, Seattle, WA 98195 (206)6164587