Prostaglandin E2 activates clusters of apical Cl- channels in principal cells via a cyclic adenosine monophosphate-dependent pathway
| Autor: | Brian N. Ling, K E Kokko, D C Eaton |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Kidney Cortex Thapsigargin Calcium-Transporting ATPases Dinoprostone Membrane Potentials chemistry.chemical_compound Chloride Channels Internal medicine Cyclic AMP medicine Animals Cyclic adenosine monophosphate Kidney Tubules Collecting Transcellular Reversal potential Cells Cultured Membrane potential Forskolin Terpenes Cell Membrane Colforsin Electric Conductivity General Medicine Apical membrane Arginine Vasopressin Endocrinology Bucladesine chemistry Chloride channel Biophysics Rabbits Research Article |
| Zdroj: | Journal of Clinical Investigation. 93:829-837 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci117037 |
| Popis: | We examined cell-attached patches on principal cells of primary cultured, rabbit cortical collecting tubules. Under basal conditions, apical 9-pS Cl(-)-selective channels were observed in 9% of patches (11/126), and number of channels times open probability (NP0) was 0.56 +/- 0.21. The channel had a linear current-voltage relationship, reversal potential (Erev) near resting membrane potential, a P0 (0.30-0.70) that was independent of voltage, and complicated kinetics (i.e., bursting) at hyperpolarized potentials. NP0 and channel frequency were increased after 30 min of basolateral exposure to 0.5 microM PGE2 (18/56), 10 microM forskolin (23/36), or 0.5 mM dibutyryl cyclic adenosine monophosphate (cAMP) (25/41). Increases in NP0 appeared to be mediated primarily through an increase in the number of observed channels per patch (N), not changes in P0. After these cAMP-increasing maneuvers, N was inconsistent with a uniform distribution of channels in the apical membrane (P < 0.001), but rather the channels appeared to be clustered in pairs. Apical 0.5 microM PGE2 (12/91), apical or basolateral 0.5 microM PGF2 alpha (8/110), or 0.25 microM thapsigargin (releaser of intracellular Ca2+ stores) (7/73) did not increase NP0 or channel frequency. Conclusions: (a) 9-pS Cl- channels provide a conductive pathway for apical membrane Cl- transport across principal cells. (b) Channel activation by basolateral PGE2 is mediated via a cAMP-, but not a Ca(2+)-dependent mechanism. (c) Apical channels are clustered in pairs. (d) With its low baseline frequency and Erev near resting membrane potential, this channel would not contribute significantly to transcellular Cl- flux under basal conditions. (e) However, cAMP-producing agonists (i.e., PGE2, arginine vasopressin) would increase apical Cl- transport with the direction determined by the apical membrane potential. |
| Databáze: | OpenAIRE |
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