Study Finds that Intercalated Cell BK Channels Have an Important Role in Flow-Induced Potassium Secretion

August 31, 2020

Study Abstract

Urinary potassium secretion in the aldosterone-sensitive distal nephron (ASDN) is mediated by two potassium secretory channels, a low conductance renal outer medullary potassium (ROMK) channel and a high-conductance Ca2+-, voltage-, and stretch-active BK channel. Evidence suggests that these two channels mediate renal potassium secretion, with the ROMK channel mediating constitutive potassium secretion while the ibertiotoxin-sensitive BK channel, composed of pore-forming α subunits as well as accessory subunits, mediates flow-induced potassium secretion. Both of these channels play a major role in renal adaptation to dietary potassium.

ROMK channels are restricted to principal cells, but conducting BK channels have been detected in both principal cells and acid-base transporting intercalated cells in the mammalian ASDN. The major question motivating this study is whether flow-induced potassium secretion or renal adaptation to dietary potassium are mediated by intercalated cells and/or principal cells in BK channels.

To directly address the above question, Evan C. Ray, MD, PhD, Arohan R. Subramanya, MD, and Thomas R. Kleyman, MD, participated in a study with colleagues at the University of Pittsburgh, Lisa M. Satlin, MD, and colleagues at the Icahn School of Medicine Mount Sinai, and colleagues at the New York Medical College and the University of Utah to generate and study a mouse model with targeted disruption of the BKα subunit in intercalated cells in the ASDN.

The impact of this disruption on whole animal adaptation to dietary potassium was tested by measuring blood potassium levels and urinary potassium clearance. When placed on a high potassium diet for 13 days, the experimental group showed significantly higher levels of blood potassium levels, but only in the males. In both males and females, urinary potassium secretion rates were similar.

To test the effects of disruption on BK channel activity, charybdotoxin-sensitive whole cell potassium currents were measured in single intercalated cells and principal cells. Whole cell charybdotoxin-sensitive potassium currents were readily seen in the intercalated cells of the control group, but were largely absent in the intercalated cell population with disrupted BKα subunits. Flow-stimulated potassium transport in microperfused cortical collecting ducts (CCD) was also measured, finding flow-induced potassium secretion in CCDs isolated from controls but not in the experimental group.

These results add to the evidence that intercalated cell BK channels play an important role in flow-induced potassium secretion. It also suggests, at least in mice, that sex plays a role in adaptation to a high potassium diet.

Reference

Carrisoza-Gaytan, R., E.C. Ray, D. Flores, A.L. Marciszyn, P. Wu, L. Liu, A.R. Subramanya, W.H. Wang, S. Sheng, L.J. Nkashama, J. Chen, E.K. Jackson, S.M. Mutchler, S. Heja, D.E. Kohan, L.M. Satlin, T.R. Kleyman. Intercalated cell BKα subunit is required for flow-induced K+ secretion. JCI Insight. 5:e130553, 2020.


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