Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine
Abstract
:1. Introduction
2. Results
2.1. Baseline Na+ Absorption Mechanisms in Wild-Type Mice
2.2. Activation of SGLT1 Concomitantly Increases Mucosal to Serosal 22Na+ Fluxes under Short-Circuit Conditions
2.3. Activation of SGLT1 does not Increase Mucosal to Serosal 22Na+ Fluxes under Open-Circuit Conditions
2.4. Baseline Na+ Absorption Mechanisms in Claudin-15 Deficient Mice
2.5. Na+-Dependent Glucose Transporter SGLT1 Is Up-Regulated in Cldn15−/− Mice
2.6. Absence of Claudin-15 Increases Glucose-Induced Mucosal to Serosal 22Na+ Flux
2.7. The Efficiency of Na+ Recycling Systems Is Reduced in a Cholera Toxin-Induced Diarrhea Model
3. Discussion
3.1. Intestinal Nutrient Absorption Mechanisms Need a Large Amount of Luminal Na+
3.2. Paracellular Na+ Permeability Is Decreased in Cldn15−/− Mice
3.3. Luminal Negative Potential Is Important for Na+ Recirculation
3.4. Physiological Relevance of the Na+ Recirculation System in the Small Intestine
4. Materials and Methods
4.1. Ethical Approval
4.2. Animals
4.3. Measurement of Electrical Parameters and Unidirectional Fluxes of 22Na+ and 36Cl−
4.4. Cholera Toxin-Induced Diarrhea Model
4.5. Chemicals
4.6. Real-Time Quantitative PCR
4.7. Immunofluorescence
4.8. Statistical and Data Analyses
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
αMDG | α-methyl-d-glucose |
Gt | transmural conductance |
Isc | short-circuit current |
J | flux |
Vte | transepithelial potential difference |
MS | mucosal to serosal |
SM | serosal to mucosal |
NHE3 | Na+/H+ exchanger-3 isoform |
IBMX | isobutylmethylxanthine |
Km | Michaelis–Menten constant |
Vmax | value of the maximum change |
ORS | oral rehydration solution |
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JNa, µmol/cm2/h | Isc, µmol/cm2/h | Gt, mS/cm2 | n | |||
---|---|---|---|---|---|---|
M→S | S→M | Net | ||||
Short-Circuit Conditions | ||||||
Control | 51.4 ± 2.3 | 24.6 ± 1.7 | 26.9 ± 1.5 | 2.4 ± 0.5 | 58.7±2.2 | 4 |
S3226 | 38.9 ± 3.4 * | 28.3 ± 1.9 | 10.6 ± 3.9 * | 1.7 ± 0.2 | 54.6±2.8 | 6 |
Open-Circuit Conditions | ||||||
Control | 44.2 ± 2.6 N.S. | 22.8 ± 1.6 N.S. | 21.4 ± 3.7 N.S. | 1.8 ± 0.3 N.S. | 55.2±2.4 N.S. | 3 |
JNa, µmol/cm2/h | Isc, µmol/cm2/h | Gt, mS/cm2 | n | |||
---|---|---|---|---|---|---|
M→S | S→M | Net | ||||
Short-Circuit Conditions | ||||||
Control | 31.9 ± 1.9 † | 10.4 ± 0.8 † | 21.4 ± 2.4 | 3.3 ± 0.4 † | 17.7 ± 0.7 † | 6 |
S3226 | 22.3 ± 1.5 * | 5.8 ± 0.5 * | 16.4 ± 1.0 | 3.9 ± 0.1 | 13.6 ± 1.0 * | 4 |
Open-Circuit Conditions | ||||||
Control | 35.6 ± 2.4 N.S. | 12.0 ± 0.9 N.S. | 23.7 ± 2.4 | 4.0 ± 0.6 | 19.4 ± 1.4 | 6 |
JNa, µmol/cm2/h | Isc, µmol/cm2/h | Gt, mS/cm2 | n | |||
---|---|---|---|---|---|---|
M→S | S→M | Net | ||||
Open-Circuit Conditions | ||||||
Control | 29.2 ± 2.1 | 18.4 ± 3.6 | 10.8 ± 2.8 | −1.0 ± 0.2 | 61.6 ± 9.3 | 3 |
Cholera | 16.9 ± 1.4* | 17.3 ± 1.4 | −0.3 ± 1.0 * | 3.9± 0.3 * | 39.6 ± 1.1 * | 5 |
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Nakayama, M.; Ishizuka, N.; Hempstock, W.; Ikari, A.; Hayashi, H. Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine. Int. J. Mol. Sci. 2020, 21, 376. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020376
Nakayama M, Ishizuka N, Hempstock W, Ikari A, Hayashi H. Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine. International Journal of Molecular Sciences. 2020; 21(2):376. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020376
Chicago/Turabian StyleNakayama, Michiko, Noriko Ishizuka, Wendy Hempstock, Akira Ikari, and Hisayoshi Hayashi. 2020. "Na+-Coupled Nutrient Cotransport Induced Luminal Negative Potential and Claudin-15 Play an Important Role in Paracellular Na+ Recycling in Mouse Small Intestine" International Journal of Molecular Sciences 21, no. 2: 376. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020376