# Determining the role of the mechano-activated potassium channel TRAAK at nodes of Ranvier

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $74,284

## Abstract

Abstract
Action potential propagation through nodes of Ranvier is central to nervous system function. Understanding this
process is essential for developing improved treatments for nodal pathologies of electrical signaling including
multiple sclerosis, Guillain-Barré syndrome, stroke, spinal injury, and glaucoma. Saltatory conduction—the
jumping of the action potential from one node to the next—has been described since its discovery as a purely
electrical phenomenon. This proposal aims to investigate whether it is also fundamentally mechanical in nature.
The mechano-activated two-pore domain potassium channel TRAAK is exclusively expressed at nodes of
Ranvier. TRAAK is insensitive to voltage, but acutely tuned to membrane tension, with cell swelling increasing
TRAAK-mediated potassium currents up to one hundred-fold. Still, whether mechanical activation of TRAAK is
relevant to spike propagation is unknown. Using a combination of organic chemistry, molecular biophysics, and
neurophysiology, this proposal will examine how mechanically activated TRAAK currents contribute to action
potential propagation, speed, and reliability. To selectively control TRAAK channels, photoswitchable tethered
ligands (PTLs) will be designed, synthesized, and optimized for maximal spatiotemporally precise block of
TRAAK current. Screening of PTL tethering sites in leak and mechano-activated open TRAAK channels will
enable the identification of state-specific PTL·Cys-TRAAK pairs and the precise modulation of basal and/or
mechano-activated TRAAK currents. Using these tools, TRAAK's contributions to action potential propagation
will be characterized in myelinated optic nerve under typical conditions and in response to mechanical
perturbation. These experiments will both elucidate the role of TRAAK in spike propagation and, potentially,
demonstrate that mechanical force is central to node repolarization, with broad implications for the treatment of
nodal pathologies and the field of neuronal communication as a whole.

## Key facts

- **NIH application ID:** 10915430
- **Project number:** 5F32EY035182-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Anna Virginia Elleman
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915430

## Citation

> US National Institutes of Health, RePORTER application 10915430, Determining the role of the mechano-activated potassium channel TRAAK at nodes of Ranvier (5F32EY035182-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10915430. Licensed CC0.

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