Effect of dexamethasone on voltage-gated Na+ channel in cultured human bronchial smooth muscle cells

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Abstract

Voltage-gated Na+ channel (INa) encoded by SCN9A mRNA is expressed in cultured human bronchial smooth muscle cells. We investigated the effects of dexamethasone on INa, by using whole-cell voltage clamp techniques, reverse transcriptase/polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR. Acute application of dexamethasone (10− 6 M) did not affect INa. However, the percentage of the cells with INa was significantly less in cells pretreated with dexamethasone for 48 h, and the current-density of INa adjusted by cell capacitance in cells with INa was also decreased in cells treated with dexamethasone. RT-PCR analysis showed that α and β subunits mRNA of INa mainly consisted of SCN9A and SCN1β, respectively. Treatment with dexamethasone for 24-48 h inhibited the expression of SCN9A mRNA. The inhibitory effect of dexamethasone was concentration-dependent, and was observed at a concentration higher than 0.1 nM. The effect of dexamethasone on SCN9A mRNA was not blocked by spironolactone, but inhibited by mifepristone. The inhibitory effects of dexamethasone on SCN9A mRNA could not be explained by the changes of the stabilization of mRNA measured by using actinomycin D. These results suggest that dexamethasone inhibited INa encoded by SCN9A mRNA in cultured human bronchial smooth muscle cells by inhibiting the transcription via the glucocorticoid receptor.

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