Second‐generation antipsychotic quetiapine blocks voltage‐dependent potassium channels in coronary arterial smooth muscle cells

• Published in: Journal of applied toxicology Vol. 44; no. 9; pp. 1446 - 1453
• Main Authors: Zhuang, Wenwen, Mun, Seo‐Yeong, Park, Minju, Jeong, Junsu, Kim, Hye Ryung, Park, Hongzoo, Han, Eun‐Taek, Han, Jin‐Hee, Chun, Wanjoo, Li, Hongliang, Park, Won Sun
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2024
• Subjects: Antipsychotics; coronary arterial smooth muscle cell; Coronary artery; Deactivation; Electric potential; electrophysiology; Inactivation; Membrane potential; Muscles; Physiological effects; Potassium channels (voltage-gated); Psychotropic drugs; Quetiapine; Recovery time; Side effects; Smooth muscle; Voltage; voltage‐dependent K+ channel; quetiapine; coronary arterial smooth muscle cell; electrophysiology; voltage‐dependent K+ channel
• ISSN: 0260-437X; 1099-1263; 1099-1263
• DOI: 10.1002/jat.4648

Voltage‐dependent K+ (Kv) channels play an important role in restoring the membrane potential to its resting state, thereby maintaining vascular tone. In this study, native smooth muscle cells from rabbit coronary arteries were used to investigate the inhibitory effect of quetiapine, an atypical antipsychotic agent, on Kv channels. Quetiapine showed a concentration‐dependent inhibition of Kv channels, with an IC50 of 47.98 ± 9.46 μM. Although quetiapine (50 μM) did not alter the steady‐state activation curve, it caused a negative shift in the steady‐state inactivation curve. The application of 1 and 2 Hz train steps in the presence of quetiapine significantly increased the inhibition of Kv current. Moreover, the recovery time constants from inactivation were prolonged in the presence of quetiapine, suggesting that its inhibitory action on Kv channels is use (state)‐dependent. The inhibitory effects of quetiapine were not significantly affected by pretreatment with Kv1.5, Kv2.1, and Kv7 subtype inhibitors. Based on these findings, we conclude that quetiapine inhibits Kv channels in both a concentration‐ and use (state)‐dependent manner. Given the physiological significance of Kv channels, caution is advised in the use of quetiapine as an antipsychotic due to its potential side effects on cardiovascular Kv channels. The primary goal of this study was to examine the direct effect of quetiapine on vascular Kv channels. Our results indicate that quetiapine reduces Kv currents in both concentration‐ and use (state)‐dependent manners. This inhibition is characterized by a shift in the steady‐state inactivation curve, with no effect on the activation curve.