# Blood pressure regulation by smooth muscle cell ion channels

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $380,000

## Abstract

Systemic blood pressure is regulated by smooth muscle cells (myocytes) of small (resistance-size) arteries and
arterioles. A key regulator of arterial myocyte contractility is membrane potential, which is controlled by plasma
membrane ion channels. Arteries from hypertensive subjects are depolarized, leading to vasoconstriction, but
mechanisms involved in this pathological alteration are unclear. Arterial myocytes express several different
transient receptor potential (TRP) channels, but physiological systemic blood pressure regulation and
involvement of these proteins during hypertension is unclear. This lack of knowledge exists largely because
TRP subfamily expression, regulation and function in myocytes of arteries that control blood pressure is
unclear, there are no specific TRP channel modulators and global TRP channel knockout mice produced
confusing effects on blood pressure. Arterial myocytes express TRP polycystin 1 (TRPP1) channels, but blood
pressure regulation by these proteins, signaling mechanisms involved and the concept that targeting of these
proteins alleviates hypertension have not been studied. For this proposal, we created the first conditional,
myocyte-specific TRPP1 knockout (TRPP1sm-/-) mice to test these hypotheses. Cellular current (I) generated
by a membrane ion channel population is determined by number (N), open probability (Po) and single channel
current (i), such that I=N.Po.i. Previous studies have primarily examined cell currents (I) generated by TRP
channels in myocytes. In contrast, contributions of N and Po to currents are poorly understood. This
application stems from novel preliminary data suggesting that regulation of myocyte TRPP1 channel surface N
and Po controls arterial contractility and blood pressure, TRPP1 channels are upregulated during hypertension,
and myocyte-specific TRPP1 knockout alleviates hypertension. Three specific aims will be investigated. Aim 1
will examine the hypothesis that myocyte TRPP1 channels control arterial contractility and systemic blood
pressure using novel, inducible, myocyte-specific TRPP1 knockout mice. Aim 2 will investigate the hypothesis
that physiological stimuli regulate both TRPP1 channel surface abundance and open probability in myocytes to
control arterial contractility. Aim 3 will explore the hypothesis that systemic hypertension is associated with an
increase in arterial myocyte TRPP1 channel surface expression that contributes to vasoconstriction and that
myocyte-specific TRPP1 ablation attenuates hypertension. Methods used to test these hypotheses will include
arterial biotinylation, FRET, co-IP, immunofluorescence, patch-clamp electrophysiology, membrane potential
recording, intracellular Ca2+ imaging, arterial myography and blood pressure telemetry. This proposal will
provide significant novel information concerning blood pressure regulation by arterial myocyte TRPP1
channels.

## Key facts

- **NIH application ID:** 9912820
- **Project number:** 5R01HL133256-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Jonathan H Jaggar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912820

## Citation

> US National Institutes of Health, RePORTER application 9912820, Blood pressure regulation by smooth muscle cell ion channels (5R01HL133256-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9912820. Licensed CC0.

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