Volume 33, Issue 9 e14149
ORIGINAL ARTICLE

Bicarbonate ion transport by the electrogenic Na+/HCO3 cotransporter, NBCe1, is required for normal electrical slow-wave activity in mouse small intestine

Wenchang Zhao

Wenchang Zhao

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Neuroendocrine Pharmacology, China Medical University, Shenyang, China

Search for more papers by this author
Liwen Zhang

Liwen Zhang

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Neuroendocrine Pharmacology, China Medical University, Shenyang, China

Search for more papers by this author
Leonid G. Ermilov

Leonid G. Ermilov

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Search for more papers by this author
Maria Gabriela Colmenares Aguilar

Maria Gabriela Colmenares Aguilar

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Search for more papers by this author
David R. Linden

David R. Linden

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Search for more papers by this author
Seth T. Eisenman

Seth T. Eisenman

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Search for more papers by this author
Michael F. Romero

Michael F. Romero

Physiology and Biomedical Engineering, Rochester, MN, USA

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

Search for more papers by this author
Gianrico Farrugia

Gianrico Farrugia

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Search for more papers by this author
Lei Sha

Corresponding Author

Lei Sha

Neuroendocrine Pharmacology, China Medical University, Shenyang, China

Correspondence

Simon J. Gibbons, Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.

Email: [email protected]

Lei Sha, China Medical University, 77 Pu He Road, Shenbei New District, Shenyang, Liaoning Province 110122, China

Emails: [email protected]; [email protected]

Search for more papers by this author
Simon J. Gibbons

Corresponding Author

Simon J. Gibbons

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Rochester, MN, USA

Physiology and Biomedical Engineering, Rochester, MN, USA

Correspondence

Simon J. Gibbons, Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.

Email: [email protected]

Lei Sha, China Medical University, 77 Pu He Road, Shenbei New District, Shenyang, Liaoning Province 110122, China

Emails: [email protected]; [email protected]

Search for more papers by this author
First published: 10 April 2021

Wenchang Zhao and Liwen Zhang contributed equally to this work.

Funding information

This work was supported by NIH R01 DK57061 to Dr. Gibbons and Dr. Farrugia, by the Mayo Clinic Center for Cell Signaling in Gastroenterology P30DK084567, and Grant No. 81670492 from the National Natural Science Foundation of China to Dr. Lei Sha.

Abstract

Background

Normal gastrointestinal motility depends on electrical slow-wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO3 in extracellular solutions used to record slow waves indicates a role for HCO3 transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na+/HCO3 cotransporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves. This study aimed to determine how extracellular HCO3 concentrations affect electrical activity in mouse small intestine and to determine the contribution of NBCe1 activity to these effects.

Methods

Immunohistochemistry and sharp electrode electrical recordings were used.

Key Results

The NBCe1 immunoreactivity was localized to ICC-MY of the tunica muscularis. In sharp electrode electrical recordings, removal of HCO3- from extracellular solutions caused significant, reversible, depolarization of the smooth muscle and a reduction in slow-wave amplitude and frequency. In 100 mM HCO3, the muscle hyperpolarized and slow wave amplitude and frequency increased. The effects of replacing extracellular Na+ with Li+, an ion that does not support NBCe1 activity, were similar to, but larger than, the effects of removing HCO3-. There were no additional changes to electrical activity when HCO3- was removed from Li+ containing solutions. The Na+/HCO3 cotransport inhibitor, S-0859 (30µM) significantly reduced the effect of removing HCO3 on electrical activity.

Conclusions & Inferences

These studies demonstrate a major role for Na+/HCO3 cotransport by NBCe1 in electrical activity of mouse small intestine and indicated that regulation of intracellular acid:base homeostasis contributes to generation of normal pacemaker activity in the gastrointestinal tract.

DISCLOSURES

None of the authors have any relevant disclosures to declare in respect of this work.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.