Relaxation of bladder smooth muscle by flavonoids from Sophora flavescens via direct activation of the large‐conductance calcium‐activated potassium channel.

Abstract

The large‐conductance calcium‐activated potassium channel (BKCa channel) plays critical roles in smooth muscle relaxation. In urinary bladder, BKCa channel activity underlies the maintenance of the resting membrane potential and the phasic relaxation. We recently reported kurarinone, a flavonoid found in S. flavescens, as a potent activator of the BKCa channel and thus a strong relaxant of bladder smooth muscle (Lee et al., Mol. Pharmacol., 2016). Since the potentiating effects of flavonoids with similar chemical structures vary significantly, we further screen the flavonoids of S. flavescens. We newly identified three more flavonoids from S. flavescens as potent activator of BKCa channel. In particular, kuraridinol, a prenylated chalcone, strongly activates BKCa from the extracellular side by stabilizing its open conformation. This compound markedly affects the gating kinetics of the channel by stimulating faster opening and slower closing. In order to identify new potent activators of BKCa channel from other natural sources, we are currently screening a flavonoid library using a cell‐based fluorescence assay. Thus, the flavonoids can be an excellent natural source of BKCa channel activators that may be of therapeutic benefit for targeting channel activity.Support or Funding InformationKorea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries(IPET) through Agri‐Bio industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs(MAFRA)(2017‐352)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.