The voltage-sensitive sodium channel in Drosophila melanogaster is being studied using two neurotoxins, tetrodotoxin and saxitoxin, which are both known to bind specifically to sodium channels and block the action potential. A rapid filtration assay has been developed to study 3H-saxitoxin binding to extracts of Drosophila heads. Initial studies have shown that the toxin binds to Drosophila extracts with high affinity. This binding is saturable, reversible, and noncooperative, and is inhibited by low concentrations of tetrodotoxin. Saxitoxin binding will be studied in mutants which are abnormally sensitive to tetrodotoxin and in mutants which exhibit temperature-induced defects in propagation of action potentials to determine if any of these mutants are altered inthe saxitoxin-binding component of the sodium channel. Specifically, we will test for alterations in the number of binding sites as well as for alterations in other parameters including KD, offrate, and KI for inhibition by tetrodotoxin. In addition, for the temperature-sensitive mutants we will study the thermal inactivation of the binding activitiy and will define the effects of pH and temperature on the binding reaction itself. These studies provide a model system for investigating the organization of genes coding for products involved in cell excitability.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016204-07
Application #
3396745
Study Section
Genetics Study Section (GEN)
Project Start
1979-08-01
Project End
1986-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Feng, Guoping; Reale, Vincenzina; Chatwin, Heather et al. (2003) Functional characterization of a neuropeptide F-like receptor from Drosophila melanogaster. Eur J Neurosci 18:227-38
Hodges, Dianne D; Lee, Daewoo; Preston, Charles F et al. (2002) tipE regulates Na+-dependent repetitive firing in Drosophila neurons. Mol Cell Neurosci 19:402-16
Wang, X J; Reynolds, E R; Deak, P et al. (1997) The seizure locus encodes the Drosophila homolog of the HERG potassium channel. J Neurosci 17:882-90
Reale, V; Hannan, F; Hall, L M et al. (1997) Agonist-specific coupling of a cloned Drosophila melanogaster D1-like dopamine receptor to multiple second messenger pathways by synthetic agonists. J Neurosci 17:6545-53
Feng, G; Hannan, F; Reale, V et al. (1996) Cloning and functional characterization of a novel dopamine receptor from Drosophila melanogaster. J Neurosci 16:3925-33
Hannan, F; Hall, L M (1996) Temporal and spatial expression patterns of two G-protein coupled receptors in Drosophila melanogaster. Invert Neurosci 2:71-83
Smith, L A; Wang, X; Peixoto, A A et al. (1996) A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects. J Neurosci 16:7868-79
Feng, G; Deak, P; Chopra, M et al. (1995) Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function. Cell 82:1001-11
Feng, G; Deak, P; Kasbekar, D P et al. (1995) Cytogenetic and molecular localization of tipE: a gene affecting sodium channels in Drosophila melanogaster. Genetics 139:1679-88
Zheng, W; Feng, G; Ren, D et al. (1995) Cloning and characterization of a calcium channel alpha 1 subunit from Drosophila melanogaster with similarity to the rat brain type D isoform. J Neurosci 15:1132-43

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