# Control of Airway Sensory Nerve Function by Voltage-Gated Sodium Channel Subtypes

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $528,619

## Abstract

Asthma, COPD, and chronic cough, as with other visceral inflammatory diseases, are characterized by an
over-excited sensory nervous system. When airway sensory nerves are dysregulated by inflammation it can
lead to excessive coughing, dyspnea, changes in breathing pattern, and reflex bronchospasm and secretions
that can threaten lung function. Our long-range goal is to determine the ion channels and mechanisms that
underlie the excitability of each of the sensory nerve subtypes in the airways. The present proposal focuses on
voltage-gated sodium channels (NaVs). NaV are perhaps the most important ion channels regulating nerve
activity as they are required for action potential generation and conduction, and are also involved in setting the
threshold for nerve activation. There are nine NaV subtypes termed NaV1.1-1.9. This renewal proposal builds
on our seminal observations and strong progress since the original application. We now know that the three
nociceptor subtypes in the airways express almost exclusively NaV 1.7, NaV 1.8, and NaV 1.9. These
channels are not present in skeletal or cardiac muscle and are very modestly expressed in the central nervous
system. This renders them ideal targets for drugs aimed at normalizing an overactive airway sensory nervous
system. We have completed an extensive functional analysis on the role of NaV1.7 and 1.8 in regulating each
of three distinct nociceptor subtypes at the level of their terminals within the airways. In AIM I we will turn our
attention to the mechanisms by which NaV1.9 regulates the excitability of these nerves. In AIM 2 we will
evaluate genetically and functionally the NaV subtypes expressed in non-nociceptive RAR/SAR stretch
receptive fibers. In AIM 3 we will will begin our evaluation of the role of NaV1.8 and 1.9 in the airways
hyperexcitability that is associated with respiratory viral infections. In AIM 4 we will use our newly developed
extrinsically innervated isolated human bronchus to evaluate, for the first time, the translatability of the major
findings we obtain in laboratory animals to the human condition. We anticipate that this work will provide a
conceptual and rational framework with which to base future clinical studies with selective NaV1 blocking drugs
that can be applied directly to the sensory terminals in the airways with topical inhaled delivery methods.

## Key facts

- **NIH application ID:** 9984488
- **Project number:** 5R01HL122228-06
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Bradley Joel Undem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $528,619
- **Award type:** 5
- **Project period:** 2014-09-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984488

## Citation

> US National Institutes of Health, RePORTER application 9984488, Control of Airway Sensory Nerve Function by Voltage-Gated Sodium Channel Subtypes (5R01HL122228-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9984488. Licensed CC0.

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