BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway

The expression of large conductance calcium-activated potassium channels (BK channels) in adipose tissue has been identified for years. BK channel deletion can improve metabolism in vivo, but the relative mechanisms remain unclear. Here, we examined the effects of BK channels on the differentiation of adipose-derived stem cells (ADSCs) and the related mechanisms. BK alpha and beta 1 subunits were expressed on adipocytes. We found that both deletion of the KCNMA1 gene, encoding the pore forming alpha subunit of BK channels, and the BK channel inhibitor paxilline increased the expression of key genes in the peroxisome proliferator activated receptor (PPAR) pathway and promoted adipogenetic differentiation of ADSCs. We also observed that the MAPK-ERK pathway participates in BK channel deficiency-promoted adipogenic differentiation of ADSCs and that ERK inhibitors blocked the differentiation-promoting effect of BK channel deficiency. Hyperplasia of adipocytes is considered beneficial for metabolic health. These results indicate that BK channels play an important role in adipose hyperplasia by regulating the differentiation of ADSCs and may become an important target for studying the pathogenesis and treatment strategies of metabolic disorder-related diseases. BK channels can inhibit the phosphorylation of ERK, thus inhibiting the role of ERK in promoting adipogenic differentiation through PPAR gamma. Deficiency of BK can relieve the inhibition effect of BK on ERK and promote adipogenic differentiation, known as adipocyte hyerplasia.