# Molecular mechanisms of mechanosensing in the urinary tract

> **NIH NIH K99** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $91,445

## Abstract

Project Summary
 Problems with function in the lower urinary tract (LUT) are remarkably common: in adults
over 40, up to 70% of all survey respondents report LUT pathologies. This is in part because the
physiology of urination (micturition) is complex: it requires smooth muscle in the bladder and
urethra to be coordinated with activity in the voluntary, striated muscle of the urethral sphincter.
Seven peripheral reflexes enable this coordination, and all of these arise from mechanical cues
in the bladder (i.e. bladder stretch) or in the urethra (i.e. urethral fluid flow or distension).
Remarkably, we do not know the identity of the molecules or exactly which cell types sense these
mechanical forces. For example, two cell types, sensory neurons that innervate the LUT and the
urothelial cells in the bladder, are proposed to contribute to these reflexes. Therefore, the details
of how these reflexes are initiated and integrated in the system remain poorly understood.
 I hypothesize that the mechanosensory ion channels PIEZO1 and PIEZO2 mediate
mechanosensing in the lower urinary tract. I will use bladder-pressure recordings in combination
with electromyography to characterize micturition reflexes, as well as histology and behavior to
characterize the expression and the functional role of PIEZOs in urination, specifically as they
function in the urothelial cells. I will also test the role of PIEZOs in mediating bladder
accommodation responses to fluid filling, as well as their role in mediating pain during pathological
conditions like cystitis. Together, these results will delineate the contribution of the
mechanotransduction ion channels, specific cell types and peripheral circuitry that facilitate
urination. Understanding these processes is an important first step to alleviate the enormous
burden of LUT pathologies in humans.

## Key facts

- **NIH application ID:** 10192406
- **Project number:** 1K99DK128621-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Kara L Marshall
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $91,445
- **Award type:** 1
- **Project period:** 2021-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192406

## Citation

> US National Institutes of Health, RePORTER application 10192406, Molecular mechanisms of mechanosensing in the urinary tract (1K99DK128621-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10192406. Licensed CC0.

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