# Ghrelin Modulation of CaV 2.2 Channels After Spinal Cord Injury

> **NIH NIH F31** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $35,788

## Abstract

Project Summary
Gastrointestinal (GI) dysfunction after spinal cord injury (SCI) is a highly prevalent, but significantly
understudied comorbidity that negatively impacts quality of life for individuals with SCI. Increasing evidence
suggests impaired vagal activity is a primary cause of upper GI dysfunction after injury. Under normal
conditions, gastric reflexes are coordinated by the vagus nerve. The vagus nerve contains both afferent fibers that
convey sensory information to central structures and efferent fibers that carry motor output needed for gastric
contractions. Previous work in our lab has demonstrated that following injury, vagal afferents are significantly
less responsive to chemical stimuli, including the gut peptide ghrelin. Ghrelin is an orexigenic hormone that
normally serves to decrease vagal afferent activity and increase gastric motility by binding to the growth hormone
secretagogue receptor (GHSR1a), a G protein-coupled receptor, expressed along the vagal afferents. The cellular
mechanisms underlying ghrelin’s ability to modulate vagal afferent activity in both healthy and disease states
have yet to be fully elucidated. This proposal will utilize an animal model of SCI combined with molecular and
imaging techniques, in vitro patch-clamp electrophysiology, and in vivo nerve recordings to identify mechanisms
underlying the loss of vagal sensitivity post-SCI. The proposed experiments will investigate the central
hypothesis that GHSR1a-mediated inhibition of calcium currents is dysregulated in gastric-projecting nodose
ganglia neurons after SCI. Based upon our preliminary observations, we will test the hypothesis with two specific
aims. Aim 1 will determine the precise mechanism underlying GHSR1a modulation of voltage-gated Ca2+
channels (CaV2.2 or N-type) in gastric-projecting vagal afferent neurons of naïve rats using whole-cell patch-
clamp electrophysiology. Aim 2 will utilize immunohistochemistry, single-cell quantitative reverse transcription
polymerase chain reaction (qRT-PCR), electrophysiological techniques, and in vivo nerve recordings to identify
whether the GHSR1a-mediated effects of ghrelin on N-type Ca2+ channel currents and gastric vagal afferent
excitability are dysregulated following SCI. This proposal will provide critical information regarding how changes
to GPCR-mediated inhibition of CaV channels impairs gastric vagal afferent activity following injury. In addition,
the proposed work will benefit future studies investigating the use of ghrelin mimetics to treat gastric dysmotility
associated with a broad range of conditions including SCI, diabetes mellitus, and obesity.

## Key facts

- **NIH application ID:** 10838353
- **Project number:** 5F31DK136279-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Hannah J Goudsward
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $35,788
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838353

## Citation

> US National Institutes of Health, RePORTER application 10838353, Ghrelin Modulation of CaV 2.2 Channels After Spinal Cord Injury (5F31DK136279-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10838353. Licensed CC0.

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