Dietary K+ and Cl− independently regulate basolateral conductance in the principal and intercalated cells of the collecting duct

Abstract

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 Kir4.1/5.1 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 Kir4.1/5.1 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 Kir4.1/5.1 activity. Overall, our results suggest independent regulation the basolateral Kir4.1/5.1 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 InformationThis research was supported by NIH‐NIDDK DK095029 (to O. Pochynyuk), AHA‐15SDG25550150 (to M. Mamenko)