Dexamethasone-induced up-regulation of two-pore domain K+ channel genes, TASK-1 and TWIK-2, in cultured human periodontal ligament fibroblasts

摘要

Two-pore domain K+ channels are widely expressed in many types of cells, and have various important functions, especially maintaining the resting membrane potential. In the previous report, we have confirmed the presence of several kinds of two-pore domain K+ channels in the periodontal ligament (PDL) fibroblasts. It is well known that dexamethasone (Dex) regulates the functions of various kinds of ion channels. In this work, we investigate if Dex affects the gene expressions of the two-pore domain K+ channels in the PDL fibroblasts. We also examined the effects of other steroid hormones on the K+ channels gene expression. The mRNA levels of two-pore domain K+ channels in human PDL fibroblasts were examined in the presence or absence of Dex by RT-PCR. The effects of other steroid hormones (aldosterone, estrogen, 1α,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃], and retinoic acid) were also examined. Dex significantly induced the expression of TASK-1 and TWIK-2 in mRNA levels in both a dose- and a time-dependent manner. The stimulatory effects of Dex were completely abolished by a glucocorticoid receptor antagonist. 1,25-(OH)₂D₃ also increased the TASK-1 mRNA levels but had no effect on TWIK-2 expression. Dex, one of the potent glucocorticoid, probably have a protective role against external stimuli by maintaining the membrane potential of PDL fibroblasts through the up-regulation of TASK-1 and TWIK-2 K+ channels.