The Mechanosensitive BKα/β1 Channel Localizes to Cilia of Principal Cells in Rabbit Cortical Collecting Duct (CCD)
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.
Carrisoza-Gaytan, R., Wang, L., Schreck, C., Kleyman, T., Wang, W., & Satlin, L. (2017). The Mechanosensitive BKα/β1 Channel Localizes to Cilia of Principal Cells in Rabbit Cortical Collecting Duct (CCD). American Journal of Physiology.Renal Physiology, 312 (1), F143-F156. https://doi.org/10.1152/ajprenal.00256.2016