Abstract: SA-PO1061
High Cholesterol Diet (HCD) Downregulates BK Channels in the Rabbit Cortical Collecting Duct (CCD)
Session Information
- Na+, K+, Cl-
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Fluid, Electrolytes, and Acid-Base
- 703 Na+, K+, Cl- Basic
Authors
- Carrisoza-Gaytan, Rolando, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Flores, Daniel Armando, Mount Sinai School Of Medicine, New York, New York, United States
- Satlin, Lisa M., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background
The apical BK channel in the CCD mediates flow-induced K secretion (FIKS) and adaptation to K loading. Preliminary results had shown that 4-5 wks HCD increases plasma membrane cholesterol content in the CCD, blunts flow-stimulated but not basal net Na absorption (JNa), and inhibits FIKS (~37%) in rabbit CCDs. As studies in endothelial cells and osteoblasts identify genomic effects of a HCD (Physiol Genomics, 2012; Acta Pharm Sinica, 2011), we speculated that a HCD may reduce abundance of BK channels in the CCD.
Methods
NZW rabbits were randomized after weaning to receive either a standard (Base Diet; BD) or a cholesterol enriched diet (HCD; 0.3%) for 4-5 wks, at which time the animals were sacrificed. Kidneys were removed and CCDs microdissected for (i) microperfusion to measure JNa and net K secretion (JK), (ii) quantitative PCR to assess abundance of mRNA encoding Slo1 and (iii) immunoperfusion with anti-BKα Ab to examine plasma membrane expression.
Results
In 6 HCD CCDs, JNa increased from 13.3±6.6 to 30.1±8.5 pmol/min.mm (P≤0.01) in response to an increase in flow rate from 1 to 5 nl/min.mm; this flow-stimulated increase in JNa was less than observed in BD (25.9±4.3 to 73.3±7.0; n= 4; P≤0.01). In the same 6 HCD CCDs, a 5-fold increase in flow rate increased JK from -4.9±1.3 to -11.5±2.2 pmol/min.mm (P≤0.04), transport rates half those observed in BD (-11.3±4.0 to -21.2±1.6; n= 4; P≤0.03). Slo1 mRNA expression in HCD CCDs (n=6 samples; 10-20 mm total tubular length/sample) tended to be less than in BD CCDs (n=3 samples; 13-25 mm/sample; p=0.07). The relative apical/whole-cell expression of BKα was less in HCD principal (Δ=27±0.7%) and intercalated (Δ=24±1.0 %) cells than in BD cells (n=4 rabbits per diet; P≤0.001).
Conclusion
Our results suggest that HCD downregulates the transcription and apical expression of BKα and thus inhibits FIKS in the rabbit CCD. Whether HCD also reduces expression of other channels necessary for K secretion, including ENaC, ROMK and Ca2+ channels, remains to be explored.
Funding
- NIDDK Support