# Role of ASICs within sensory neurons in health and disease

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2020 · —

## Abstract

Heart failure affects ~3% of the adults and 37% of the Medicare population, and is the second leading
cause for hospitalization within VA medical centers after psychiatric illness. A hallmark of patients suffering
from chronic heart failure is dysautonomia, characterized by increased sympathetic tone and diminished
parasympathetic tone. The importance of this autonomic imbalance is highlighted by the remarkable benefits in
morbidity and mortality with the use of β-adrenergic receptor blockers. In fact, all of our most effective
pharmacological therapies to treat heart failure are targeted toward the efferent limbs of these aberrant
neurohormonal pathways. However, no new proven effective drugs to treat heart failure have come forth in last
couple of decades. How can we expand our therapies? We propose that targeting the triggers – in particular
the molecular receptors within the sensory neurons – that initiate these pathological reflexes presents a novel
strategy to abrogate the dysautonomia associated with heart failure. In fact, recent studies have shown that
inhibiting the sensory pathways that trigger this dysautonomia can have beneficial effects on this autonomic
imbalance, and improve cardiovascular function in animal models of heart failure. However, very little is known
about these sensors at the molecular level. We and others have shown that acid-sensing ion channels (ASICs)
are highly expressed in skeletal muscle and cardiac afferents, and within the carotid body, where they sense
metabolic changes associated with ischemia and exercise, and initiate reflexes to maintain homeostasis.
Accordingly, we have preliminary data demonstrating that ASICs are required for normal maximal exercise
capacity in mice, and in Aim 1 we will define the mechanism by which ASICs contribute to exercise in health.
However, these same sensory pathways are exaggerated in heart failure, and have been shown to contribute
to the chronic associated dysautonomia. Thus, we hypothesize that ASICs are major contributors to this
autonomic imbalance, and could serve as molecular targets to treat heart failure. Consistent with this
hypothesis, our preliminary data indicate that ASICs in skeletal muscle afferents have altered biophysical
properties in a mouse model of heart failure. Moreover, we have preliminary data showing that the deleterious
cardiac remodeling that occurs after myocardial infarction is abrogated in ASIC knockout mice. The Aims of
this proposal are to: 1) determine the mechanisms by which ASICs contribute to exercise physiology;
and 2) determine the contribution of ASICs to the dysautonomia associated with heart failure.
Understanding the beneficial role of ASICs during an acute stressor in health (exercise) is crucial to
understanding their potential pathological role in a chronic stress condition (heart failure). Our studies will
provide a better understanding of the molecular sensors that trigger dysautonomia, and could therefore lead to
a novel mean...

## Key facts

- **NIH application ID:** 9864012
- **Project number:** 5I01BX000776-08
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** CHRISTOPHER J BENSON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2011-10-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864012

## Citation

> US National Institutes of Health, RePORTER application 9864012, Role of ASICs within sensory neurons in health and disease (5I01BX000776-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864012. Licensed CC0.

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