Inhibition of voltage-gated potassium channel by aripiprazole in rabbit coronary arterial smooth muscle cells.
Eur J Pharmacol
; 973: 176610, 2024 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-38663541
ABSTRACT
Aripiprazole, a third-generation antipsychotic, has been widely used to treat schizophrenia. In this study, we evaluated the effect of aripiprazole on voltage-gated potassium (Kv) channels in rabbit coronary arterial smooth muscle cells using the patch clamp technique. Aripiprazole reduced the Kv current in a concentration-dependent manner with a half-maximal inhibitory concentration of 0.89 ± 0.20 µM and a Hill coefficient of 1.30 ± 0.25. The inhibitory effect of aripiprazole on Kv channels was voltage-dependent, and an additional aripiprazole-induced decrease in the Kv current was observed in the voltage range of full channel activation. The decay rate of Kv channel inactivation was accelerated by aripiprazole. Aripiprazole shifted the steady-state activation curve to the right and the inactivation curve to the left. Application of a repetitive train of pulses (1 and 2 Hz) promoted inhibition of the Kv current by aripiprazole. Furthermore, the recovery time constant from inactivation increased in the presence of aripiprazole. Pretreatment of Kv1.5 subtype inhibitor reduced the inhibitory effect of aripiprazole. However, pretreatment with Kv 7 and Kv2.1 subtype inhibitors did not change the degree of aripiprazole-induced inhibition of the Kv current. We conclude that aripiprazole inhibits Kv channels in a concentration-, voltage-, time-, and use (state)-dependent manner by affecting the gating properties of the channels.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasos Coronários
/
Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Bloqueadores dos Canais de Potássio
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Miócitos de Músculo Liso
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Aripiprazol
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Coréia do Sul
País de publicação:
Holanda