Effects of miR-200b-3p inhibition on the TRPC6 and BKCa channels of podocytes

Abstract

Transient receptor potential canonical 6 (TRPC6) and large-conductance Ca²⁺-activated K⁺ channels (BK_Ca), two of the key ion channels for blood filtration function of podocytes, have been implicated in the pathogenesis of kidney diseases. Moreover, it has been reported that miR-200 b plays an important role in regulating the biological processes of podocytes. In this study, we aimed to examine whether there was a relationship between miR-200 b-3p and the two ion channels. It was suggested that miR-200 b-3p down-regulation inhibited the currents of TRPC6 and BK_Ca channels. It also showed that miR-200 b-3p inhibition reduced the levels of protein expression and mRNA transcription of TRPC6 and BK_Ca channels. Moreover, the down-regulation of miR-200 b-3p resulted in the decrease of the intracellular Ca²⁺ concentration. It was also suggested that the decrease of BK_Ca currents resulting from miR-200 b-3p inhibition could be regulated by TRPC6 channels. TRPC6 blockage also inhibited BK_Ca currents and reduced the level of BK_Ca expression. These results together suggested that miR-200 b-3p inhibition reduced the currents of TRPC6, which led to the decrease of intracellular Ca²⁺ concentration. The decrease of Ca²⁺ source required for BK_Ca activation may result in the inhibition of BK_Ca currents.

Keywords: BK(Ca); Ca(2+); Podocytes; TRPC6.