# Endogenous Ion Channel Activity Tracers to Monitor the Involvement of Kv2 Channels During Ischemic Attack

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $30,319

## Abstract

Project Summary/Abstract
Endogenous Ion Channel Activity Tracers to Monitor the Involvement of Kv2 Channels During Ischemic Attack
 Neuronal electrical signals are governed by the combined action of many ion channel subtypes.
Different sets of ion channels sum to create a remarkable diversity in neuronal electrical excitability. However,
due to technological limitations, dissecting the individual role of an ion channel subtype during a complex
physiological or pathophysiological event remains difficult. Consequently we have a limited understanding of
how the electrical dynamics of individual endogenous ion channel subtypes contribute to global signals,
especially in intact tissue or in live animals. Technology developed in Dr. Jon Sack’s lab offers an opportunity
to image the activity of ion channel subtypes throughout a complex tissue. Specifically, these
Kv2 Activity Tracers (KATs) report activation of endogenous neuronal potassium voltage-gated ion channels of
subtype 2. We have engineered these KATs for 2-photon imaging, and demonstrated that KATs can report
activation endogenous neuronal Kv2 ion channels in brain slices. I propose to measure activation of a specific
ion channel subtype in tissue slices and live animals under pathophysiological ischemic stress that mimics
stroke. In the brain, Kv2 ion channels are highly expressed in most, if not all neurons. Kv2 channels are
proposed to be crucial to suppress excitotoxic signaling events during many stresses, including ischemic
attack. Previous studies have suggested that Kv2 ion channels become very active during ischemia, suppress
electrical excitability, and provide neural protection from excitotoxic signaling. However, there has also been
evidence that excessive efflux of potassium through Kv2 channels during ischemia can trigger apoptotic
cascades leading to neuronal death. Both of these proposed roles assume a dramatic increase in the number
of active Kv2 channels, yet this has never been observed in real time in complex tissues. For my doctoral
studies I will probe a mechanism for mass activation, and image changes in Kv2 ion channel activity in models
of ischemic stroke. My results will improve our understanding of the molecular mechanisms leading to neuronal
cells death following stroke, and whether Kv2 channels are a potential drug target to increase neuronal survival
following stroke. Further, my research will be the first attempt at using fluorescent probes to measure
conformational change of specific ion channels in intact tissue and potentially transform the way protein
activation is studied in a physiological context. Throughout this project the sponsor/co-sponsor team, will
implement a comprehensive training plan focused on improving critical thinking, experimental and analytical
skills, presentation and public speaking skills, and aid in creating a network of colleagues and collaborators.

## Key facts

- **NIH application ID:** 10128513
- **Project number:** 5F31NS108614-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Rebecka Jane Sepela
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,319
- **Award type:** 5
- **Project period:** 2019-04-02 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128513

## Citation

> US National Institutes of Health, RePORTER application 10128513, Endogenous Ion Channel Activity Tracers to Monitor the Involvement of Kv2 Channels During Ischemic Attack (5F31NS108614-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128513. Licensed CC0.

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