Premium
Dietary K + and Cl− independently regulate basolateral conductance in the principal and intercalated cells of the collecting duct
Author(s) -
Zaika Oleg,
Tomilin Viktor,
Mamenko Mykola,
Pochynyuk Oleh
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.856.14
Subject(s) - chemistry , intercalated cell , conductance , biophysics , reabsorption , epithelial polarity , potassium channel , hyperpolarization (physics) , medicine , patch clamp , endocrinology , homeostasis , membrane potential , biochemistry , kidney , membrane , biology , cell , stereochemistry , receptor , mathematics , combinatorics , nuclear magnetic resonance spectroscopy
Kidneys play a central role in maintaining systemic homeostasis by matching dietary variations of electrolyte intake with their excretion in urine. Final adjustments take place in the collecting duct where transport rates are highly sensitive to electrolyte intake. The collecting duct comprises of electrically uncoupled principal and intercalated cells mediating Na + /K + exchange and Cl − reabsorption, respectively. Basolateral membrane conductance sets up an electrochemical driving force governing electrolyte transport. Previous work established that potassium K ir 4.1/5.1 channels underlie basolateral conductance in principal cells, whereas ClC‐K2 channels are essential for basolateral Cl − flux in intercalated cells. However, little is known whether variations in dietary K + and Cl − affect activity of these channels. Using patch clamp electrophysiology at the single channel and whole cell levels in freshly isolated mouse collecting ducts, we found a marked upregulation of the basolateral K + ‐selective current and hyperpolarization of basolateral membrane potential in principal cells of mice subjected to a high (5%) K + diet for one week compared to the control. This stimulation stemmed from the significantly increased functional levels of K ir 4.1/5.1 but not from channel open probability. When high K + was accompanied with Cl − , this led to drastically decreased basolateral Cl − ‐selective current, the number of active ClC‐K2 and reduced channel open probability in intercalated cells. In contrast, when high K + was given as citrate, ClC‐K2 macroscopic current and channel activity were significantly increased. Consistently, dietary Cl − restriction with regular K + augmented ClC‐K2‐dependent conductance but had little effect on K ir 4.1/5.1 activity. Overall, our results suggest independent regulation the basolateral K ir 4.1/5.1 and ClC‐K2 in principal and intercalated cells by dietary K + and Cl − . We propose that this mechanism contributes to precise tuning of urinary excretion in response to variable dietary electrolyte intake. Support or Funding Information This research was supported by NIH‐NIDDK DK095029 (to O. Pochynyuk), AHA‐15SDG25550150 (to M. Mamenko)