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Associate Professor, Molecular and Integrative Physiology and Biophysics
B.S. and Ph.D, University of Buenos Aires (Argentina)
Molecular Mechanisms of Neurotransmitter-gated Ion Channels
The laboratory is broadly interested in the relationship between structure and function in neurotransmitter-gated ion channels, with special emphasis on the Cys-loop superfamily of synaptic receptor-channels. Our main tools are single-channel recording and analysis, and protein engineering techniques. Some of the particular issues we have been working on lately are:
Quantitative characterization of fundamental properties of neurotransmitter-gated ion channels such as rate and equilibrium constants of ligand binding in the closed and open states.
Quantitative understanding of the different phenomena that contribute to the kinetics of the postsynaptic-current decay.
Linear free-energy relationships and the dynamics of the closed <--> open conformational change.
Elenes S, Decker M, Cymes GD, and Grosman, C. 2009. Decremental response to high-frequency trains of acetylcholine pulses but unaltered fractional Ca2+ currents in a panel of 'slow-channel syndrome' nicotinic receptor mutants. Journal of General Physiology, 133:151-69
Cymes GD and Grosman C. 2008. Pore-opening mechanism of the nicotinic acetylcholine receptor evinced by proton transfer. Nature Structural and Molecular Biology (15)4:389-396.
Elenes S, Ni Y, Cymes GD, and Grosman C. 2006. Desensitization contributes to the synaptic response of gain-of-function mutants of the muscle nicotinic receptor. Journal of General Physiology 128:615-627.
Purohit Y and Grosman C. 2006. Block of muscle nicotinic receptors by choline suggests that the activation and desensitization gates act as distinct molecular entities. Journal of General Physiology 127:703-717.
Purohit Y and Grosman C. 2006. Estimating binding affinities of the nicotinic receptor for low-efficacy ligands using mixtures of agonists and two-dimensional concentration-response relationships." Journal of General Physiology 127:719-735.
Cymes GD, Ni Y, and Grosman C. 2005. Probing ion-channel pores one proton at a time. Nature 438:975-980.
Grosman C. 2003. Free-energy landscapes of ion-channel gating are malleable: Changes in the number of bound ligands are accompanied by changes in the location of the transition state in acetylcholine receptor channels. Biochemistry 42:14977-14987.
Related Research (By Area):
Cell Signaling and Communication
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