# Spectroscopic analyses of TRPV1 during gating

> **NIH NIH R21** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $432,218

## Abstract

The transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel essential to the cellular
mechanism underlying the detection of noxious stimuli. TRPV1 is activated by heat, protons, capsaicin, and
animal toxins, and is modulated by proalgesic inflammatory agents (e.g., bradykinin, bioactive lipids) produced
in response to tissue injury. Our long-term goal is to delineate the roles of polymodal ion channels in sensory
neuron excitation and the mechanisms by which they contribute to inflammatory pain. The rationale for our
proposed research is that a deeper mechanistic understanding of TRPV1 proton- and heat-dependent gating
would greatly facilitate the development of strategies to ameliorate TRPV1-mediated inflammatory pain, without
disrupting normal sensory physiology. While functional and structural characterization of TRPV1 have shed light
on the mechanisms of capsaicin and toxin activation, the processes whereby the two main endogenous
activators, protons and heat, trigger gating remain largely unknown. Moreover, the intracellular TRPV1 C
terminus is a key regulatory site for regulating stimulus sensitivity. However, any potential allosteric interacting
regions or putative contacts with the plasma membrane have yet remain to be explored. It is our contention that
spectroscopic approaches are needed to fully define the allosteric conformational changes responsible for
TRPV1 activation and to depict the C-terminal/membrane interaction. To this end, we will carry out
electrophysiological analyses together with electron paramagnetic resonance spectroscopy experiments in both
closed and open states. With these data, we will depict the conformational changes that TRPV1 undergoes
during proton- and heat-dependent gating. We will pursue two Specific Aims: 1) Determine the dynamic
conformational rearrangements of TRPV1 during proton and heat activation, and 2) Explore the interaction
between the TRPV1 C-terminal domain and the plasma membrane. The proposed research is significant
because it is expected to have broad translational importance in the treatment of pain associated with a wide
range of pathophysiological conditions.

## Key facts

- **NIH application ID:** 10039442
- **Project number:** 1R21NS117873-01
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Julio Francisco Cordero-Morales
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,218
- **Award type:** 1
- **Project period:** 2020-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039442

## Citation

> US National Institutes of Health, RePORTER application 10039442, Spectroscopic analyses of TRPV1 during gating (1R21NS117873-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10039442. Licensed CC0.

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