| dc.contributor.author | Wei-Ting Chang | |
| dc.contributor.author | Sheng-Nan Wu | |
| dc.contributor.other | Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan | |
| dc.contributor.other | Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan | |
| dc.date.accessioned | 2025-10-09T05:31:10Z | |
| dc.date.available | 2025-10-09T05:31:10Z | |
| dc.date.issued | 01-04-2021 | |
| dc.identifier.uri | https://www.mdpi.com/1424-8247/14/5/388 | |
| dc.identifier.uri | http://digilib.fisipol.ugm.ac.id/repo/handle/15717717/41117 | |
| dc.description.abstract | QO-40 (5-(chloromethyl)-3-(naphthalene-1-yl)-2-(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-7(4<i>H</i>)-one) is a novel and selective activator of KCNQ2/KCNQ3 K<sup>+</sup> channels. However, it remains largely unknown whether this compound can modify any other type of plasmalemmal ionic channel. The effects of QO-40 on ion channels in pituitary GH<sub>3</sub> lactotrophs were investigated in this study. QO-40 stimulated Ca<sup>2+</sup>-activated K<sup>+</sup> current (<i>I</i><sub>K(Ca)</sub>) with an EC<sub>50</sub> value of 2.3 μM in these cells. QO-40-stimulated <i>I</i><sub>K(Ca)</sub> was attenuated by the further addition of GAL-021 or paxilline but not by linopirdine or TRAM-34. In inside-out mode, this compound added to the intracellular leaflet of the detached patches stimulated large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK<sub>Ca</sub>) channels with no change in single-channel conductance; however, there was a decrease in the slow component of the mean closed time of BK<sub>Ca</sub> channels. The <i>K</i><sub>D</sub> value required for the QO-40-mediated decrease in the slow component at the mean closure time was 1.96 μM. This compound shifted the steady-state activation curve of BK<sub>Ca</sub> channels to a less positive voltage and decreased the gating charge of the channel. The application of QO-40 also increased the hysteretic strength of BK<sub>Ca</sub> channels elicited by a long-lasting isosceles-triangular ramp voltage. In HEK293T cells expressing <i>α-hSlo</i>, QO-40 stimulated BK<sub>Ca</sub> channel activity. Overall, these findings demonstrate that QO-40 can interact directly with the BK<sub>Ca</sub> channel to increase the amplitude of <i>I</i><sub>K(Ca)</sub> in GH<sub>3</sub> cells. | |
| dc.language.iso | EN | |
| dc.publisher | MDPI AG | |
| dc.subject.lcc | Medicine | |
| dc.title | Effective Activation of BK<sub>Ca</sub> Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4<i>H</i>)-one), Known to Be an Opener of KCNQ2/Q3 Channels | |
| dc.type | Article | |
| dc.description.keywords | OQ-40 (5-(chloromethyl)-3-(naphthalene-1-yl)-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-7-(4<i>H</i>)-one) | |
| dc.description.keywords | Ca<sup>2+</sup>-activated K<sup>+</sup> current | |
| dc.description.keywords | large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel | |
| dc.description.keywords | single-channel kinetics | |
| dc.description.keywords | hysteresis | |
| dc.description.doi | 10.3390/ph14050388 | |
| dc.title.journal | Pharmaceuticals | |
| dc.identifier.e-issn | 1424-8247 | |
| dc.identifier.oai | oai:doaj.org/journal:fd2e42c04e8c478383e7c3241241b9f3 | |
| dc.journal.info | Volume 14, Issue 5 | |
