Asenapine, an atypical antipsychotic, blocks voltage-gated potassium channels in rabbit coronary artery smooth muscle cells.

Autor: Seo MS; Department of Physiology, Konkuk University School of Medicine, Chungju, 27478, South Korea. Electronic address: seoms@kangwon.ac.kr., Kang M; Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea., An JR; Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea., Heo R; Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea., Jung WK; Department of Biomedical Engineering, And Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, 48513, South Korea., Choi IW; Department of Microbiology, College of Medicine, Inje University, Busan, 48516, South Korea., Han ET; Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea., Han JH; Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea., Chun W; Department of Pharmacology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea., Park WS; Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address: parkws@kangwon.ac.kr.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2022 Nov 05; Vol. 934, pp. 175318. Date of Electronic Publication: 2022 Oct 07.
DOI: 10.1016/j.ejphar.2022.175318
Abstrakt: We investigated the effect of asenapine, a commonly used atypical antipsychotic, on voltage-dependent K + (Kv) channels in rabbit coronary artery smooth muscle cells. Asenapine inhibited the Kv current in a concentration-dependent manner, with an half-inhibitory concentration (IC 50 ) value of 8.59 ± 2.25 μM and Hill coefficient of 0.64 ± 0.06. Although asenapine did not affect the steady-state activation curve of Kv channels, it shifted the voltage dependence of the steady-state inactivation curve toward a more negative potential. Asenapine increased the recovery time constant of channel inactivation and produced use (state)-dependent inhibition of Kv channels at a stimulation frequency of 1 or 2 Hz. Pretreatment with the Kv1.5 subtype inhibitor DPO-1 reduced the Kv current; however, additional application of asenapine did not further inhibit the Kv current. Pretreatment with the Kv2.1 subtype inhibitor guangxitoxin and Kv7 inhibitor linopirdine also reduced the Kv current. However, additional application of asenapine further reduced the Kv current, similar to the application of asenapine alone. Asenapine induced membrane depolarization and vasoconstriction. Based on these results, we conclude that asenapine inhibits the Kv current in concentration- and use (state)-dependent manners by shifting the inactivation curve. The major target of asenapine is the Kv1.5 subtype channel.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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