# Dynamics Of Ligand Gated Ion Channels

> **NIH NIH R35** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $767,214

## Abstract

PROJECT SUMMARY/ABSTRACT
 Glutamate receptors mediate the spread of excitation in the mammalian central nervous system, and
ultimately control physiological functions such as movement and cognition. They are classified into four
subfamilies: N-methyl-D-aspartate (NMDA), -amino-5-methyl-3-hydroxy-4-isoxazole propionate (AMPA),
kainate, and delta receptors. All four subtypes are topologically similar, comprising four protein subunits held
together as a dimer-of-dimers. However, their gating characteristics and mechanisms are unique, reflecting
distinct roles in synaptic transmission. The goal of my laboratory is to understand the mechanisms that underlie
the functional fine-tuning of each of these subtypes. Using a multipronged approach that combines biochemical,
electrophysiological, fluorescence, and computational methods, we have already identified conformational
transitions that are critical for mediating activation and inhibition of AMPA and NMDA glutamate receptors.
However, a direct understanding of how such structural changes in one part of the protein control changes in
other parts, and how they dictate functional properties, remains unknown. We propose to develop and use
multicolor single-molecule fluorescence resonance energy transfer (FRET) to draw structure–function
correlations between different segments of each glutamate receptor subtype. We will also focus our efforts on
understanding the less well-studied kainate and delta subtypes. Specifically, we will investigate the mechanisms
underlying activation and modulation of an abundant form of the kainate receptor by agonists, ions, and auxiliary
proteins. In addition, we have preliminary data showing that delta receptor function is dependent on connections
with trans-synaptic protein complexes, therefore we will study the structure and function of delta receptors in the
context of synaptic binding partners. Together, these investigations will place our fundamental single-molecule
investigations in a physiological context, and eventually allow us to understand functional differences between
synaptic and non-synaptic glutamate receptors.

## Key facts

- **NIH application ID:** 10330310
- **Project number:** 2R35GM122528-06
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Vasanthi Jayaraman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $767,214
- **Award type:** 2
- **Project period:** 2017-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330310

## Citation

> US National Institutes of Health, RePORTER application 10330310, Dynamics Of Ligand Gated Ion Channels (2R35GM122528-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330310. Licensed CC0.

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