Inhibition of voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells by the atypical antipsychotic agent sertindole.
J Appl Toxicol
; 44(3): 391-399, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-37786982
ABSTRACT
The regulation of membrane potential and the contractility of vascular smooth muscle cells (VSMCs) by voltage-dependent K+ (Kv) potassium channels are well-established. In this study, native VSMCs from rabbit coronary arteries were used to investigate the inhibitory effect of sertindole, an atypical antipsychotic agent, on Kv channels. Sertindole induced dose-dependent inhibition of Kv channels, with an IC50 of 3.13 ± 0.72 µM. Although sertindole did not cause a change in the steady-state activation curve, it did lead to a negative shift in the steady-state inactivation curve. The application of 1- or 2-Hz train pulses failed to alter the sertindole-induced inhibition of Kv channels, suggesting use-independent effects of the drug. The inhibitory response to sertindole was significantly diminished by pretreatment with a Kv1.5 inhibitor but not by Kv2.1 and Kv7 subtype inhibitors. These findings demonstrate the sertindole dose-dependent and use-independent inhibition of vascular Kv channels (mainly the Kv1.5 subtype) through a mechanism that involves altering steady-state inactivation curves. Therefore, the use of sertindole as an antipsychotic drug may have adverse effects on the cardiovascular system.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antipsychotic Agents
/
Potassium Channels, Voltage-Gated
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Imidazoles
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Indoles
Limits:
Animals
Language:
En
Journal:
J Appl Toxicol
Year:
2024
Type:
Article
Affiliation country:
South Korea