Going with the flow: New insights regarding flow induced K+ secretion in the distal nephron

Abstract

Abstract K+ secretion in the distal nephron has a critical role in K+ homeostasis and is the primary route by which K+ is lost from the body. Renal K+ secretion is enhanced by increases in dietary K+ intake and by increases in tubular flow rate in the distal nephron. This review addresses new and important insights regarding the mechanisms underlying flow‐induced K+ secretion (FIKS). While basal K+ secretion in the distal nephron is mediated by renal outer medullary K+ (ROMK) channels in principal cells (PCs), FIKS is mediated by large conductance, Ca2+/stretch activated K+ (BK) channels in intercalated cells (ICs), a distinct cell type. BK channel activation requires an increase in intracellular Ca2+ concentration ([Ca2+]i), and both PCs and ICs exhibit increases in [Ca2+]i in response to increases in tubular fluid flow rate, associated with an increase in tubular diameter. PIEZO1, a mechanosensitive, nonselective cation channel, is expressed in the basolateral membranes of PCs and ICs, where it functions as a mechanosensor. The loss of flow‐induced [Ca2+]i transients in ICs and BK channel‐mediated FIKS in microperfused collecting ducts isolated from mice with IC‐specific deletion of Piezo1 in the CCD underscores the importance of PIEZO1 in the renal regulation of K+ transport.

Keywords

• BK channels
• Calcium signaling
• Mechanotransduction
• PIEZO1
• TRPV4