Authors
Wenwen Zhuang, Hye Ryung Kim, Sooa Lee, Seungjoo Kim, Seokhun Jeong, Daeun Shin, Mi Seon Seo, Jin Ryeol An, Hongzoo Park, Eun-Taek Han, Jin-Hee Han, Wanjoo Chun, Se Jin Lee, Hongliang Li, Won Sun Park
Published in
Toxicology and applied pharmacology. Pages 118116. Nov 10, 2026. Epub Nov 10, 2026.
Abstract
Voltage-gated K+ (Kv) channels are crucial for regulating membrane potential and contractility in vascular smooth muscle cells (VSMCs). In this study, we investigated the effects of the third-generation antipsychotic brexpiprazole on Kv channels in native VSMCs isolated from rabbit coronary arteries. Brexpiprazole inhibited Kv currents in a concentration-dependent manner, with an IC50 of 8.35 ± 2.61 μM and a Hill coefficient of 0.81 ± 0.07. This inhibition was accompanied by an accelerated inactivation rate and a leftward shift of the steady-state inactivation curve. Repetitive stimulation at 1 and 2 Hz enhanced the inhibitory effect, and recovery from inactivation was significantly prolonged, indicating use-dependent blockade. Pharmacological analysis further implied subtype specificity, as inhibition was attenuated by pretreatment with diphenyl phosphine oxide-1 (a Kv1.5-selective blocker) but not by stromatoxin-1 (Kv2.1) or linopirdine (Kv7). Taken together, these findings indicate that Kv1.5 contributes to the brexpiprazole-sensitive Kv current and that brexpiprazole suppresses Kv currents through both concentration- and state-dependent mechanisms, at least in part by altering channel inactivation properties.
PMID:
43009072
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.
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