# Investigating the role of NBCe1-B in renal and cardiac acid-base handling

> **NIH NIH F30** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $36,638

## Abstract

Project Summary
 An estimated 15% of U.S. adults are estimated to have chronic kidney disease (CKD), with cardiovascular
disease (CVD) the greatest cause of death in this population. Metabolic acidosis is common in CKD, and has
deleterious effects on both the kidney and the heart. Complicating our understanding and limiting our ability to
prevent these effects are gaps in our knowledge of the integrated cardiorenal response to acidosis, which is
largely influenced by cellular level acid-base transporters. The Na+/HCO3- co-transporter (NBCe1-B) is one such
transporter. There is accumulating evidence that NBCe1-B is involved in the renal response to acidosis and the
pathophysiologic development of cardiac hypertrophy, but the consequence of NBCe1-B loss on these systems
has never been tested at the whole animal level. The goal of this project is to determine the role of NBCe1-B in
the kidney and heart by comparing the renal and cardiac phenotypes of wild-type (WT) and NBCe1-B knockout
(KO) mice. The over-arching hypothesis of this proposal is that NBCe1-B is essential for renal (Aim 1) and
cardiac (Aim 2) acid-base handling. The purpose of Aim 1 is to determine the abundance, distribution, and
function of NBCe1-B in the WT mouse kidney during acid-challenged conditions. This work will include a series
of western-blot and fluorescent immunohistochemistry experiments as well as a comparison of renal acid-base
handling during acidosis in WT and NBCe1-B KO mice as assessed by blood-gas parameters, ammonia
excretion, and titratable acid excretion. The purpose of Aim 2 is to determine the exact type and mechanism of
cardiac impairment in NBCe1-B-KO mice. The mice will receive a cardiac work-up similar to patients with heart-
failure, incorporating electrocardiogram, echocardiogram, and left-ventricular pressure catheterization
measurements. Cellular level investigation of cardiomyocytes will include histological analysis, molecular
assessment for evidence of pro-hypertrophic mechanisms using Western blot and RT-qPCR, and evaluation of
Ca2+ handling in isolated cardiomyocytes using Ca2+ sensitive microscopy. The experiments outlined in this
proposal will determine the role of NBCe1-B in the renal and cardiac systems, providing insights into the
cardiorenal response to acidosis. This work will take place at the University at Buffalo, Jacobs School of Medicine
and Biomedical Sciences (JSMBS), in the laboratory of Dr. Mark Parker, who is an expert in ion transport and
pH regulation. The training plan is tailored for development as a physician-scientist in the field of nephrology,
and will include clinical preceptorships in nephrology and cardiology in order to gain cross-disciplinary
experience, reflecting the research goals of this proposal. These longitudinal clinical preceptorships will be with
successful physician-scientists, who will also be directly involved in the proposed research, thereby providing
integrated mentorship over the course of the fellow...

## Key facts

- **NIH application ID:** 10068891
- **Project number:** 1F30DK126330-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Clayton Timothy Brady
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,638
- **Award type:** 1
- **Project period:** 2020-08-07 → 2025-08-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068891

## Citation

> US National Institutes of Health, RePORTER application 10068891, Investigating the role of NBCe1-B in renal and cardiac acid-base handling (1F30DK126330-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10068891. Licensed CC0.

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