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Kidney Week

Abstract: FR-PO609

The Stimulatory Role of SPAK Kinase in the Regulation of the Large Conductance Ca2+-Activated Potassium (BK) Channels Protein Expression in Kidney

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Bi, Ye, Emory University, Atlanta, Georgia, United States
  • Luo, Tongwang, Emory University, Atlanta, Georgia, United States
  • Li, Chunmei, Emory University, Atlanta, Georgia, United States
  • Feng, Xiuyan, LSU Shreveport , Shreveport, Louisiana, United States
  • Cai, Hui, Emory University School of Medicine, Atlanta, Georgia, United States
Background

SPS1-related proline/alanine-rich kinase (SPAK) and the oxidative stress-responsive kinase 1 (OSR1) have been shown to be the downstream kinases of with-no-lysine (WNK). SPAK/OSR1 has been shown to mediate the regulation of WNK kinase in cation-chloride cotransporter including sodium chloride cotransporter (NCC) and potassium chloride cotransporter (KCC), etc. In addition, previous studies reported that WNK4 inhibits BK channel activity and protein expression by enhancing BK degradation through stimulating ERK 1/2 and p38 signaling pathway. One previous study showed that SPAK/OSR1 suppressed BK channel activity in Xenopus oocytes over-expressing SPAK/OSR1. It remains largely unknown whether SPAK/OSR1 modulate the BK protein expression in kidney tissues. Thus, in this study we have investigated the effects of SPAK kinase on renal BK protein expressions in both mammalian cells and mouse kidney.

Methods

SPAK KO mice, ERK1 global KO mice, western blot analysis, cell culture, and siRNA knock-down experiments were used in this study.

Results

When Cos-7 and HEK 293 cells were over-expressed with SPAK plasmids, BK protein expressions were increased while decreasing ERK 1/2 phosphorylation in a dose-dependent manner, whereas the cells were transfected with SPAK siRNA, BK protein expressions were decreased while increasing ERK 1/2 phosphorylation in a dose-dependent manner. In SPAK mice, BK protein abundance was decreased while increasing ERK 1/2 phosphorylation. In addition, in ERK 1 KO mice BK protein abundance was increased while dramatically increasing SPAK phosphorylation. In addition, WNK4 inhibited BK protein expression while increasing ERK 1/2 phosphorylation.

Conclusion

These data suggested that SPAK signaling positively regulates BK protein expression through negatively modulating ERK 1/2 phosphorylation, potentially by reducing BK degradation.

Funding

  • Veterans Affairs Support