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 BKα (pore-forming subunit) and functional BK channel activity than detected in PCs, and an increase in IC BKα 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 BKα- and β1-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.
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
Rolando
R
Carrisoza-Gaytán
Department of Pharmacology, New York Medical College, Valhalla, New York.
Lijun
L
Wang
Servicio de Nefrologia-Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Carlos
C
Schreck
Departments of Medicine, Cell Biology, and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
Thomas R
TR
Kleyman
Department of Pharmacology, New York Medical College, Valhalla, New York.
Wen-Hui
WH
Wang
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York; lisa.satlin@mssm.edu.
Lisa M
LM
Satlin
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D005260:Female; D007672:Kidney Cortex / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D009399:Nephrons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits
D051036:Large-Conductance Calcium-Activated Potassium Channels; D011188:Potassium; D002118:Calcium
Ca2+ channel; Ca2+ signaling; dietary K+ adaptation; flow-induced K+ secretion; intercalated cell; maxi K channel