NYMC Faculty Publications

Title

The Mechanosensitive BKα/β1 Channel Localizes to Cilia of Principal Cells in Rabbit Cortical Collecting Duct (CCD)

Document Type

Article

Publication Date

January 2017

Department

Pharmacology

Abstract

Within the CCD of the distal nephron of the rabbit, the BK (maxi K) channel mediates Ca2+.- and/or stretch-dependent flow-induced K+. secretion (FIKS) and contributes to K+. adaptation in response to dietary K+. loading. An unresolved question is whether BK channels in intercalated cells (ICs) and/or principal cells (PCs) in the CCD mediate these K+. secretory processes. In support of a role for ICs in FIKS is the higher density of immunoreactive apical BKalpha (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKalpha expression in response to a high-K+. diet. PCs possess a single apical cilium which has been proposed to serve as a mechanosensor; direct manipulation of cilia leads to increases in cell Ca2+. concentration, albeit of nonciliary origin. Immunoperfusion of isolated and fixed CCDs isolated from control K+.-fed rabbits with channel subunit-specific antibodies revealed colocalization of immunodetectable BKalpha- and beta1-subunits in cilia as well as on the apical membrane of cilia-expressing PCs. Ciliary BK channels were more easily detected in rabbits fed a low-K+. vs. high-K+. diet. Single-channel recordings of cilia revealed K+. channels with conductance and kinetics typical of the BK channel. The observations that 1) FIKS was preserved but 2) the high-amplitude Ca2+. peak elicited by flow was reduced in microperfused CCDs subject to pharmacological deciliation suggest that cilia BK channels do not contribute to K+. secretion in this segment, but that cilia serve as modulators of cell signaling.

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