Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption
| Autor: | Henry J. Binder, Sam X. Cheng, Lieqi Tang, Scott A. Rivkees, Steven Parrish Winesett, Catherine Y. Cheng, Xiefan Fang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel Male Physiology lcsh:Medicine Sodium Chloride Physical Chemistry Biochemistry Epithelium Amiloride Rats Sprague-Dawley chemistry.chemical_compound Benzamil Glyburide Medicine and Health Sciences Lipid Hormones lcsh:Science Aldosterone Bumetanide Multidisciplinary Chemistry Barium Physical Sciences Anatomy medicine.drug Research Article inorganic chemicals Anions medicine.medical_specialty Colon Crypt Surgical and Invasive Medical Procedures digestive system 03 medical and health sciences Organ Culture Techniques Chlorides Internal medicine medicine Epithelial Sodium Channel Blockers Animals Epithelial Sodium Channels Secretion Nutrition Ions Ussing chamber Functional Electrical Stimulation lcsh:R Sodium Chemical Compounds Biology and Life Sciences Transport inhibitor Hormones Diet Gastrointestinal Tract 030104 developmental biology Endocrinology Biological Tissue chemistry Gene Expression Regulation Biophysics lcsh:Q Salts Cotransporter Physiological Processes Digestive System |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 2, p e0171045 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 μM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption. |
| Databáze: | OpenAIRE |
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