Distinct regulation of the basolateral conductance in the collecting duct by Na+ and K+ intake

Abstract

Distal renal tubule segments, such as the collecting duct, underlie final regulation of electrolyte transport to maintain systemic homeostasis. The collecting duct comprises of principal and intercalated cells having primarily Kir4.1/5.1‐mediated potassium and ClC‐K2‐dependent chloride basolateral conductance, respectively. Both dietary potassium load and sodium restriction are known to stimulate apical electrogenic Na+ reabsorption via ENaC. However, little is known whether this also affects ion fluxes across the basolateral membrane. 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. Moreover, elevated dietary potassium intake drastically decreased basolateral Cl−‐selective current and the number of active ClC‐K2 channels in intercalated cells. On the contrary, dietary Na+ restriction (<0.01% Na+) for one week had a minor effect on the basolateral K+ current and single channel Kir4.1/5.1 activity in the principal cells but significantly stimulated Cl− current and increased ClC‐K2 levels in intercalated cells. We conclude that this different response of the basolateral K+ and Cl− conductance may in part underlie the preferential Na+/K+ exchange observed during dietary K+ load and net Na+ and Cl− reabsorption to protect the circulating volume upon reduced sodium intake.