# Molecular Identity and Physiological Function of Novel Chloride Channels

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2020 · $158,316

## Abstract

PROJECT SUMMARY/ABSTRACT (R35 GM124824)
Chloride is the most abundant free anion in animal cells. It's not surprising that chloride channels are
involved in a wide range of functions as diverse as cell volume regulation, epithelial fluid secretion, regulation
of electrical excitability, and acidification of intracellular organelles. Their physiological function is
impressively illustrated by many diseases (channelopathies) caused by chloride channel mutations, such as
cystic fibrosis (1 in 2,000 Caucasians), myotonia, kidney stones, and osteopetrosis. However, despite recent
progress, chloride channels are considerably under-studied compared to their cation (sodium, potassium,
and calcium) channel cousins. Many electrophysiologically well characterized chloride channels still lack
molecular identity. Several factors block progress in this field. Unlike cation channels, there are no sequence
homologies (for example, conserved pore-lining motif) among known chloride channel families. The lack of
specific high-affinity channel ligands (e.g. toxins) hinders direct purification. Expression cloning, an
otherwise powerful technique, is hampered by high endogenous expression of channel channels in popular
expression systems. The absence of molecular identity presents the biggest roadblock to elucidate the
precise biological function of these widely expressed pore-forming membrane proteins. The proposed
research program will combine increasingly powerful genomics tools (including bioinformatics, proteomics
and gene manipulation) with electrophysiology and imaging techniques to identify novel chloride channels
and investigate their physiological function using mouse models. Our results will shed light on the molecular
identity and function of new chloride channels and may provide therapeutic strategies to target them for
diseases with abnormal chloride transport and homeostasis.

## Key facts

- **NIH application ID:** 10135581
- **Project number:** 3R35GM124824-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Zhaozhu Qiu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,316
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135581

## Citation

> US National Institutes of Health, RePORTER application 10135581, Molecular Identity and Physiological Function of Novel Chloride Channels (3R35GM124824-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135581. Licensed CC0.

---

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