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Updated: Jul 19, 2026
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Standardized Measurement of Nasal Membrane Transepithelial Potential Difference (NPD)
Published on: September 13, 2018
Examining basal chloride transport using the nasal potential difference response in a murine model
K G Brady1, T J Kelley, M L Drumm
1Center for Human Genetics, Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106-4948, USA.
Summary
Cystic fibrosis impairs chloride transport. This study reveals that while forskolin-induced responses are CFTR-dependent, chloride gradient responses involve additional channels, suggesting distinct mechanisms in cystic fibrosis transmembrane conductance regulator (CFTR) function.
Area of Science:
- Physiology
- Molecular Biology
- Medical Research
Background:
- Cystic fibrosis (CF) epithelia exhibit impaired chloride secretion.
- Nasal transepithelial potential difference (TEPD) assays assess CFTR-dependent transport defects.
- Mechanisms underlying chloride gradient-induced transport in CFTR dysfunction are unclear.
Purpose of the Study:
- To compare in vivo TEPD responses to low chloride and forskolin in mice.
- To investigate the pharmacological profiles of these responses using channel inhibitors.
- To determine if CFTR is the sole mediator of chloride transport in response to a gradient.
Main Methods:
- In vivo nasal TEPD measurements in inbred mice.
- Assessment of responses to a low chloride environment.
- Evaluation of forskolin-stimulated TEPD.
- Pharmacological profiling with chloride channel inhibitors (DIDS, DPC, glibenclamide, NPPB) and a PKA inhibitor (Rp-cAMPS).
Main Results:
- TEPD responses to low chloride and forskolin showed poor correlation within and between mouse strains.
- Distinct pharmacological profiles were observed for DIDS and Rp-cAMPS between the two response types.
- Inhibitor sensitivity suggests CFTR-independent pathways contribute to the low chloride response.
Conclusions:
- CFTR-mediated chloride transport is distinct from chloride gradient-induced transport.
- Additional chloride channels, beyond CFTR, play a role in regulating chloride transport under gradient conditions.
- These findings highlight the complexity of epithelial chloride transport in cystic fibrosis models.
