Potassium channels in intestinal epithelial cells and their pharmacological modulation: a systematic review

Author:

Cosme Dina12,Estevinho Maria Manuela13ORCID,Rieder Florian45,Magro Fernando126ORCID

Affiliation:

1. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal

2. MedInUP, Center for Drug Discovery and Innovative Medicines, Porto, Portugal

3. Department of Gastroenterology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal

4. Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases, and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio

5. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio

6. Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal

Abstract

Several potassium channels (KCs) have been described throughout the gastrointestinal tract. Notwithstanding, their contribution to both physiologic and pathophysiologic conditions, as inflammatory bowel disease (IBD), remains underexplored. Therefore, we aim to systematically review, for the first time, the evidence on the characteristics and modulation of KCs in intestinal epithelial cells (IECs). PubMed, Scopus, and Web of Science were searched to identify studies focusing on KCs and their modulation in IECs. The included studies were assessed using a reporting inclusiveness checklist. From the 745 identified records, 73 met the inclusion criteria; their reporting inclusiveness was moderate-high. Some studies described the physiological role of KCs, while others explored their importance in pathological settings. Globally, in IBD animal models, apical KCa1.1 channels, responsible for luminal secretion, were upregulated. In human colonocytes, basolateral KCa3.1 channels were downregulated. The pharmacological inhibition of K2P and Kv influenced intestinal barrier function, promoting inflammation. Evidence suggests a strong association between KCs expression and secretory mechanisms in human and animal IECs. Further research is warranted to explore the usefulness of KC pharmacological modulation as a therapeutic target.

Funder

Fundação para a Ciência e a Tecnologia

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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