NYMC Faculty Publications
Piezo1 Is a Distal Nephron Mechanosensor and Is Required for Flow-Induced K+ Secretion
Author Type(s)
Faculty
Journal Title
The Journal of Clinical Investigation
Document Type
Article
Publication Date
3-1-2024
Department
Pharmacology
Abstract
Ca2+-activated BK channels in renal intercalated cells (ICs) mediate luminal flow-induced K+ secretion (FIKS), but how ICs sense increased flow remains uncertain. We examined whether PIEZO1, a mechanosensitive Ca2+-permeable channel expressed in the basolateral membranes of ICs, is required for FIKS. In isolated cortical collecting ducts (CCDs), the mechanosensitive cation-selective channel inhibitor GsMTx4 dampened flow-induced increases in intracellular Ca2+ concentration ([Ca2+]i), whereas the PIEZO1 activator Yoda1 increased [Ca2+]i and BK channel activity. CCDs from mice fed a high-K+ (HK) diet exhibited a greater Yoda1-dependent increase in [Ca2+]i than CCDs from mice fed a control K+ diet. ICs in CCDs isolated from mice with a targeted gene deletion of Piezo1 in ICs (IC-Piezo1-KO) exhibited a blunted [Ca2+]i response to Yoda1 or increased flow, with an associated loss of FIKS in CCDs. Male IC-Piezo1-KO mice selectively exhibited an increased blood [K+] in response to an oral K+ bolus and blunted urinary K+ excretion following a volume challenge. Whole-cell expression of BKα subunit was reduced in ICs of IC-Piezo1-KO mice fed an HK diet. We conclude that PIEZO1 mediates flow-induced basolateral Ca2+ entry into ICs, is upregulated in the CCD in response to an HK diet, and is necessary for FIKS.
Recommended Citation
Carrisoza-Gaytan, R., Mutchler, S. M., Carattino, F., Soong, J., Dalghi, M. G., Wu, P., Wang, W., Apodaca, G., Satlin, L. M., & Kleyman, T. R. (2024). Piezo1 Is a Distal Nephron Mechanosensor and Is Required for Flow-Induced K+ Secretion. The Journal of Clinical Investigation, 134 (5). https://doi.org/10.1172/JCI174806
