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

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, Ca/stretch activated K (BK) channels in intercalated cells (ICs), a distinct cell type. BK channel activation requires an increase in intracellular Ca concentration ([Ca]), and both PCs and ICs exhibit increases in [Ca] 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 [Ca] 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.