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The inhibitory effect of ziprasidone on voltage-dependent K+ channels in coronary arterial smooth muscle cells.

Abstract：

:We investigated the effect of ziprasidone, a widely used treatment for schizophrenia, on voltage-dependent K+ (Kv) channels of coronary arterial smooth muscle cells using the patch-clamp technique. Ziprasidone dose-dependently inhibited Kv channels with an IC50 value of 0.39 ± 0.06 μM and a Hill coefficient of 0.62 ± 0.03. Although ziprasidone had no effect on the steady-state inactivation kinetics of the Kv channels, the steady-state activation curve shifted towards a more positive potential. These results suggest that ziprasidone inhibits Kv channels by targeting their voltage sensors. The recovery time constant of Kv channel inactivation was increased in the presence of ziprasidone. Furthermore, application of train steps (of 1 and 2 Hz) in the presence of ziprasidone led to a progressive increase in the blockade of Kv currents, suggesting that ziprasidone-induced inhibition of Kv channels is use (state)-dependent. Pretreatment with Kv1.5, Kv2.1, and Kv7 subtype inhibitors partially suppressed the ziprasidone-induced inhibition of Kv currents. These results suggest that ziprasidone inhibits vascular Kv channels through its effect on gating properties. The Kv channel-inhibiting action of ziprasidone is concentration- and use (state)-depedent.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

An JR,Seo MS,Jung HS,Heo R,Kang M,Ha KS,Park H,Park WS

doi

10.1016/j.bbrc.2020.06.038

subject

Has Abstract

pub_date

2020-08-20 00:00:00

pages

191-197

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)31245-6

journal_volume

529

pub_type

杂志文章

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