G-protein Pathway Suppressor 2 (GPS2) enhanced the renal large conductance Ca2+ activated potassium channel expression via inhibiting ERK 1/2 signaling pathway.

In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In HEK BK stably-expressing cells transfected with either GPS2 or its pCMV vector control, a single cell recording showed that GPS2 significantly increased BK channel activity (NPo), increasing BK open probability (Po) and channel number (N) compared to the control. In Cos-7 cells and HEK293T cells, GPS2 overexpression significantly enhanced the total protein expression of BK in a dose-dependent manner. Knockdown of GPS2 expression significantly decreased BK protein expression while increasing ERK1/2 phosphorylation. Knockdown of ERK1/2 expression reversed the GPS2 siRNA-mediated inhibition of BK protein expression in Cos-7 cells. Pretreatments of Cos-7 cells with either the lysosomal inhibitor, Bafilomycin A1, or the proteasomal inhibitor, MG132, partially reversed the inhibitory effects of GPS2 siRNA on BK protein expression. In addition, feeding a high potassium diet (HKD) significantly increased both GPS2 and BK protein abundance in mice. These data suggest that GPS2 enhances BK channel activity and its protein expression by reducing ERK1/2 signaling-mediated degradation of the channel. PMID: 29767559 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research