Intercalated cell BKα subunit is required for flow-induced K+ secretion
Rolando Carrisoza-Gaytan, … , Lisa M. Satlin, Thomas R. Kleyman
Rolando Carrisoza-Gaytan, … , Lisa M. Satlin, Thomas R. Kleyman
Published April 7, 2020
Citation Information: JCI Insight. 2020;5(8):e130553. https://doi.org/10.1172/jci.insight.130553.
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Research Article Cell biology Nephrology

Intercalated cell BKα subunit is required for flow-induced K+ secretion

Abstract

BK channels are expressed in intercalated cells (ICs) and principal cells (PCs) in the cortical collecting duct (CCD) of the mammalian kidney and have been proposed to be responsible for flow-induced K+ secretion (FIKS) and K+ adaptation. To examine the IC-specific role of BK channels, we generated a mouse with targeted disruption of the pore-forming BK α subunit (BKα) in ICs (IC-BKα–KO). Whole cell charybdotoxin–sensitive (ChTX-sensitive) K+ currents were readily detected in control ICs but largely absent in ICs of IC-BKα–KO mice. When placed on a high K+ (HK) diet for 13 days, blood [K+] was significantly greater in IC-BKα–KO mice versus controls in males only, although urinary K+ excretion rates following isotonic volume expansion were similar in males and females. FIKS was present in microperfused CCDs isolated from controls but was absent in IC-BKα–KO CCDs of both sexes. Also, flow-stimulated epithelial Na+ channel–mediated (ENaC–mediated) Na+ absorption was greater in CCDs from female IC-BKα–KO mice than in CCDs from males. Our results confirm a critical role of IC BK channels in FIKS. Sex contributes to the capacity for adaptation to a HK diet in IC-BKα–KO mice.

Authors

Rolando Carrisoza-Gaytan, Evan C. Ray, Daniel Flores, Allison L. Marciszyn, Peng Wu, Leah Liu, Arohan R. Subramanya, WenHui Wang, Shaohu Sheng, Lubika J. Nkashama, Jingxin Chen, Edwin K. Jackson, Stephanie M. Mutchler, Szilvia Heja, Donald E. Kohan, Lisa M. Satlin, Thomas R. Kleyman

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Figure 6

Effect of targeted deletion of BKα in intercalated cells on flow-induced increases in fura 2 fluorescence intensity ratio (FIR), a measure of intracellular Ca2+ concentration ([Ca2+]i), in microperfused CCDs.

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Effect of targeted deletion of BKα in intercalated cells on flow-induced...
(A and B) Summary tracings, representing the average fura 2 FIRs recorded in individual cells (number of cells in parentheses in 3 CCDs per genotype) prior to and following an acute increase in flow rate. The FIR in intercalated (IC, red) and principal (PC, blue) cells in fura 2–loaded CCDs isolated from male (A) and female (B) floxed control (solid lines) and IC-BKα–KO (dashed lines) mice were normalized to the FIR measured immediately prior to the increase in flow rate. An acute increase in luminal flow rate led to a typical biphasic response including an immediate rapid increase in FIR to a peak value within ~10 seconds, presumably secondary to basolateral Ca2+ entry and release of Ca2+ from internal stores, followed by a gradual decay to a plateau value that exceeds baseline for at least 120 seconds of sustained high flow. The latter plateau elevation in FIR is believed to represent mechano-induced Ca2+ influx into cells. No significant differences in the immediate peak response or the plateau elevation in FIR were detected in each individual cell type between control and IC-BKα–KO mice. (C) Data were thus pooled; graph presents the change in FIR from baseline of all cells studied in male (open circle) and female (closed circle) mice at intervals following an acute increase in flow rate. The elevation of FIR at 15, 30, 60 and 90 seconds after high flow was initiated was greater in females (n = 6 mice) compared males (n = 6 mice, P ≤ 0.05). Number of cells studied in 3 CCDs per genotype is given in parentheses. Mean ± SD. *P < 0.05 female versus male at specific times (sec), 2-tailed unpaired Student’s t test.