Abstract

The central observation upon which this proposal is based is that in embryonic amphibian muscle cells, acetylcholine receptor channels of similar conductance have multiple kinetic forms.
The specific aims are: 1) to quantify the molecular rate constants which govern transmitter binding and channel gating in different kinetic forms of channel, 2) to determine if channels can change kinetic mode, either as individuals or as a population, and 3) to ascertain if and how kinetic hererogeneity in cholinergic channels relates to myocyte development and the assembly of the neuromuscular synapse. The major experimental method will be patch clamp electrophysiology and single-channel data analysis. The research is significant because it will compliment studies of structure-function relationships in cholinergic channels, it will give insight into the molecular and cellular mechanisms by which an ion channel's kinetic properties are modulated, and it will provide a high resolution view of changes in the properties of a transmitter-gated ion channel during muscle and synapse development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023513-02
Application #
3407095
Study Section
Physiology Study Section (PHY)
Project Start
1987-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
State University of New York at Buffalo
Department
Type
Schools of Arts and Sciences
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260

  Publications

Gupta, Shaweta; Chakraborty, Srirupa; Vij, Ridhima et al. (2017) A mechanism for acetylcholine receptor gating based on structure, coupling, phi, and flip. J Gen Physiol 149:85-103
Purohit, Prasad; Chakraborty, Srirupa; Auerbach, Anthony (2015) Function of the M1 ?-helix in endplate receptor activation and desensitization. J Physiol 593:2851-66
Auerbach, Anthony (2015) Agonist activation of a nicotinic acetylcholine receptor. Neuropharmacology 96:150-6
Purohit, Prasad; Bruhova, Iva; Gupta, Shaweta et al. (2014) Catch-and-hold activation of muscle acetylcholine receptors having transmitter binding site mutations. Biophys J 107:88-99
Nayak, Tapan K; Bruhova, Iva; Chakraborty, Srirupa et al. (2014) Functional differences between neurotransmitter binding sites of muscle acetylcholine receptors. Proc Natl Acad Sci U S A 111:17660-5
Purohit, Prasad; Gupta, Shaweta; Jadey, Snehal et al. (2013) Functional anatomy of an allosteric protein. Nat Commun 4:2984
Purohit, Prasad; Auerbach, Anthony (2013) Loop C and the mechanism of acetylcholine receptor-channel gating. J Gen Physiol 141:467-78
Jadey, Snehal; Purohit, Prasad; Auerbach, Anthony (2013) Action of nicotine and analogs on acetylcholine receptors having mutations of transmitter-binding site residue ýýG153. J Gen Physiol 141:95-104
Gupta, Shaweta; Purohit, Prasad; Auerbach, Anthony (2013) Function of interfacial prolines at the transmitter-binding sites of the neuromuscular acetylcholine receptor. J Biol Chem 288:12667-79
Auerbach, Anthony (2013) The energy and work of a ligand-gated ion channel. J Mol Biol 425:1461-75

Showing the most recent 10 out of 52 publications