# The Role of Endothelial TRPC3 Channels in Neurovascular Coupling

> **NIH NIH R03** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $141,071

## Abstract

This R03 application focuses on the finding that deletion of a single ion channel gene in endothelial cells
suppresses epileptic seizures in mice. As background, it is known that cerebral blood flow (CBF) initially
increases in response to status epilepticus (SE) due to the high neuronal energy demand. But this adaptive
increase in CBF dissipates during SE progression, and despite continued high neuronal metabolism, small
cerebral arteries and arterioles begin to inappropriately constrict to limit CBF to the challenged neurons. This
pathogenic vasoconstriction, termed the “inverse hemodynamic response” (IHR), is thought to contribute to the
progression of SE and its sequela of neuronal cell death. The mechanism of IHR is unknown. However, we
have observed that Cre-mediated deletion of cation-conducting TRPC3 channels in endothelial cells prevents
the IHR during SE and reduces susceptibility to pilocarpine-induced SE. In other words, deletion of a single
TRPC channel isoform only in endothelial cells appears to exert a profound effect on neurovascular coupling
and seizure susceptibility. This proposal seeks to generate an inducible and brain-specific endothelial TRPC3
knockout line and to use this novel mouse line to elucidate the role of TRPC3 channels expressed in cerebral
vasculature endothelial cells in SE-induced IHR. Two aims will generate and characterize the inducible and
brain-specific endothelial TRPC3 knockout line using the Slco1c1-CreERT2 driver line, and determine the role
of brain endothelial cells in normal neurovascular coupling and SE-induced IHR. The studies rely on
complementary areas of expertise pooled by a research team with expertise in epilepsy, vascular ion channels,
and cerebrovascular reactivity. Techniques include immunohistochemistry, evaluation of changes in cerebral
blood flow using laser speckle contrast imaging, and two-photon imaging of cerebral vasculatures. The findings
of this project will yield a novel mouse line for the investigation of the functional role of cerebral vascular
endothelial TRPC3 channels and will provide preliminary data for a future R01 project that will determine the
underlying mechanisms of SE-induced IHR.

## Key facts

- **NIH application ID:** 9955819
- **Project number:** 1R03NS116498-01
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** FANG ZHENG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $141,071
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955819

## Citation

> US National Institutes of Health, RePORTER application 9955819, The Role of Endothelial TRPC3 Channels in Neurovascular Coupling (1R03NS116498-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9955819. Licensed CC0.

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