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Abnormal electrophysiological properties in sensory neurons from a swine model of cystic fibrosis

Date

2020-09-11

Journal Title

Journal ISSN

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ORCID

Type

Thesis

Degree Level

Masters

Abstract

Cystic fibrosis (CF) results from dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. CF has traditionally been considered a pediatric disease, but the median predicted survival age in Canada is 55 years. As a result, patients are more likely to experience chronic complications of CF. One such complication is abnormal function of the peripheral nervous system, i.e., peripheral neuropathy. Recent findings from a swine model of CF (CFTR-/-), shows these animals are born with peripheral neuropathy. However, whether a lack of CFTR expression directly affects neuronal function remains to be explored. We hypothesize that the lack of functional CFTR in sensory neurons leads to electrophysiological abnormalities that contribute to the pathology of CF. We propose that malfunction in dorsal root ganglion (DRG) neurons innervating the GI tract contributes to gut-related complications. Using patch clamp electrophysiology, we found that DRG neurons from CFTR-/- (CF) swine had reduced generation of action potentials, compared to wild-type (WT) swine. Additionally, we observed a reduced percentage of neurons with T-type calcium currents in the CF swine, with respect to WT at postnatal day 7. Furthermore, our study showed that DRG neurons from CF swine, which displayed T-type calcium currents, had abnormal activation (G/Gmax) and inactivation () kinetics. Moreover, DRG neurons from CF swine showed a reduction in capsaicin-evoked currents with respect to WT, at both postnatal day 0 and 7. Taken together our data indicate that lack of CFTR expression in sensory neurons is linked to a depression of sensory function in DRG neurons in the first week postnatal. Our data strongly suggest that in addition to the effects of CF in epithelial cells, impairments in sensory neurons may contribute to the pathology of CF.

Description

Keywords

cystic fibrosis, neuropathy

Citation

Degree

Master of Science (M.Sc.)

Department

Physiology

Program

Physiology

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DOI

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