# Renal ion channels in the control of blood pressure

> **NIH NIH R35** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $587,314

## Abstract

Project Summary
Ion channels are well recognized as important therapeutic targets because they play a crucial role in controlling
a very wide spectrum of physiological processes. Human genetic studies identified a number of mutations in
the renal ion channels leading to renal pathophysiology and abnormal changes in blood pressure.
Understanding the basic mechanisms of ion channel regulation in the kidney and how alterations of such
regulatory networks lead to water and electrolyte imbalance is fundamentally important for understanding of
the development of hypertension and designing new strategies for treating this devastating and costly disease.
The PI's research group has made key contributions in revealing specific mechanisms controlling several ion
channels in the kidney and their contribution to the development of hypertension. Given the strong historical
precedent that exists for discovering and commercializing successful drugs that modulate the activity of
sodium, calcium, or potassium channels, and considering the critical role of renal ion channels in the control of
blood pressure, new generations of therapeutic agents are expected to result from targeting ion channels in the
kidney. The central tenet of this proposal is that several types of transporters, specifically ENaC,
Kcnj10/Kcn16, Trpc6, and Clcn6, work either individually or in complex, interdependent combinations to
delicately modulate the pressure natriuresis relationship and control blood pressure, respectively. The
channels listed above were selected because either human mutations were reported in genes encoding these
channels, or they were identified by Genome Wide Association Studies as genes associated with blood
pressure control. Genomic modulation of channels and their regulators will be performed in the Dahl Salt-
Sensitive (SS) rat, a well characterized and established model, which shares many features with salt-sensitive
hypertension in humans. SS rat has been an enormously useful model as it is naturally occurring and
recapitulates the major phenotypes found in hypertensive African Americans. Importantly, the SS model has
been amenable to robust, cutting-edge genetic approaches to successfully create multiple mutant models,
which will be used in this study. Considering the availability of these unique genetic rat models and novel
approaches developed in my laboratory, I will be able to systematically study critical changes in corresponding
ion transport mechanisms and downstream signaling pathways in the setting of salt-induced hypertension.
The overall goal of this R35 proposal is to understand the impact of specific human gene variations on ion
channel function and contribute to our understanding of the role of renal ion channels in normal and
pathophysiological control of blood pressure.

## Key facts

- **NIH application ID:** 10075953
- **Project number:** 5R35HL135749-05
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Alexander Staruschenko
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $587,314
- **Award type:** 5
- **Project period:** 2017-01-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075953

## Citation

> US National Institutes of Health, RePORTER application 10075953, Renal ion channels in the control of blood pressure (5R35HL135749-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10075953. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*