Differential effects of extracellular ATP on chloride transport in cortical collecting duct cells
| Autor: | Paru P. Kathpalia, Madhumitha Rajagopal, Alan C. Pao, Jonathan Widdicombe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Epithelial sodium channel
P2Y receptor Kidney Cortex Physiology Chloride Cell Line chemistry.chemical_compound Mice Absorptiometry Photon Adenosine Triphosphate Chlorides Chloride Channels medicine Extracellular Animals Bestrophins Kidney Tubules Collecting Epithelial Sodium Channels Eye Proteins Anoctamin-1 Biological Transport Neoplasm Proteins medicine.anatomical_structure Biochemistry chemistry Gene Expression Regulation Cell culture Receptors Purinergic P2Y Chloride channel Biophysics Call for Papers Adenosine triphosphate Duct (anatomy) medicine.drug |
| Popis: | Extracellular ATP in the cortical collecting duct can inhibit epithelial sodium channels (ENaC) but also stimulate calcium-activated chloride channels (CACC). The relationship between ATP-mediated regulation of ENaC and CACC activity in cortical collecting duct cells has not been clearly defined. We used the mpkCCDc14cortical collecting duct cell line to determine effects of ATP on sodium (Na+) and chloride (Cl−) transport with an Ussing chamber system. ATP, at a concentration of 10−6M or less, did not inhibit ENaC-mediated short-circuit current ( Isc) but instead stimulated a transient increase in Isc. The macroscopic current-voltage relationship for ATP-inducible current demonstrated that the direction of this ATP response changes from positive to negative when transepithelial voltage ( Vte) is clamped to less than −10 mV. We hypothesized that this negative Vtemight be found under conditions of aldosterone stimulation. We next stimulated mpkCCDc14cells with aldosterone (10−6M) and then clamped the Vteto −50 mV, the Vteof aldosterone-stimulated cells under open-circuit conditions. ATP (10−6M) induced a transient increase in negative clamp current, which could be inhibited by flufenamic acid (CACC inhibitor) and BAPTA-AM (calcium chelator), suggesting that ATP stimulates Cl−absorption through CACC. Together, our findings suggest that the status of ENaC activity, by controlling Vte, may dictate the direction of ATP-stimulated Cl−transport. This interplay between aldosterone and purinergic signaling pathways may be relevant for regulating NaCl transport in cortical collecting duct cells under different states of extracellular fluid volume. |
| Databáze: | OpenAIRE |
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