Enhancing effects of salicylate on quinidine-induced block of human wild type and LQT3 related mutant cardiac Na+ channels.
Enhancing effects of salicylate on quinidine-induced block of human wild type and LQT3 related mutant cardiac Na+ channels.
复制标题
水杨酸盐对奎尼丁诱导的人类野生型和 LQT3 相关突变心脏 Na 通道阻断的增强作用。
DOI：
10.2220/biomedres.32.303
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
I. Hisatome
中科院分区：
文献类型：
--
作者：
T. Urashima;Y. Kurata;J. Miake;Masaru Kato;Kazuyoshi Ogura;A. Yano;M. Adachi;Yasunori Tanaka;K. Yamada;T. Hamada;E. Mizuta;M. Kuwabara;Masahiko Kato;Yasutaka Yamamoto;K. Ogino;Akio Yoshida;Y. Shirayoshi;I. Hisatome
目前尚不清楚水杨酸盐是否以状态依赖和组织特异性的方式增强抗心律失常药物对人钠离子通道的作用。因此，我们研究了水杨酸盐对奎尼丁诱导的人心肌和骨骼肌钠离子通道阻断的影响。人心肌野生型(HH1)、LQT3相关突变体(Δkpq)和骨骼肌(HSkM1)Na+通道α亚基在COS7细胞中表达。采用全细胞膜片钳技术，观察水杨酸盐对奎尼丁诱发的紧张性和使用依赖性钠通道电流的影响。在-100 mV的保持电位(HP)下，水杨酸能增强奎尼丁诱发的HH1和hSkM1电流的紧张性和使用依赖性阻断，但在-140 mV时不能。水杨酸盐在-100 mV的高压下降低奎尼丁诱导的HH1紧张性阻断的IC50值，并使奎尼丁存在时HH1的稳态失活曲线负移。根据调制受体理论，水杨酸盐可能降低奎尼丁与失活态通道结合的解离常数。此外，水杨酸盐显著增强奎尼丁诱导的紧张性和使用依赖性阻断峰电流和稳态Δ钾通道电流。结果提示，水杨酸盐通过增加奎尼丁对灭活状态通道的亲和力而增强奎尼丁对Na+通道的阻断作用。
It is unknown whether salicylate enhances the action of antiarrhythmic agents on human Na+ channels with state dependency and tissue specificity. We therefore investigated effects of salicylate on quinidine-induced block of human cardiac and skeletal muscle Na+ channels. Human cardiac wild-type (hH1), LQT3-related mutant (ΔKPQ), and skeletal muscle (hSkM1) Na+ channel α subunits were expressed in COS7 cells. Effects of salicylate on quinidine-induced tonic and use-dependent block of Na+ channel currents were examined by the whole-cell patch-clamp technique. Salicylate enhanced the quinidine-induced tonic and use-dependent block of both hH1 and hSkM1 currents at a holding potential (HP) of -100 mV but not at -140 mV. Salicylate decreased the IC50 value for the quinidine-induced tonic block of hH1 at an HP of -100 mV, and produced a negative shift in the steady-state inactivation curve of hH1 in the presence of quinidine. According to the modulated receptor theory, it is probable that salicylate decreases the dissociation constant for quinidine binding to inactivated-state channels. Furthermore, salicylate significantly enhanced the quinidine-induced tonic and use-dependent block of the peak and steady-state ΔKPQ channel currents. The results suggest that salicylate enhances quinidine-induced block of Na+ channels via increasing the affinity of quinidine to inactivated state channels.
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影响因子：
3.6
作者：
C. Starmer;A. Grant
通讯作者：
C. Starmer;A. Grant
DOI：
10.1016/s0021-9258(17)43460-0
发表时间：
1984-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Hartshorne;W. Catterall
通讯作者：
R. Hartshorne;W. Catterall
I(C) 类抗心律失常药氟卡尼优先阻断 LQT3 DeltaKPQ 突变体中的晚期钠电流。
DOI：
--
发表时间：
2000
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Nagatomo,T;January,CT;Makielski,JC
通讯作者：
Makielski,JC
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Messner,DJ;Catterall,WA
通讯作者：
Catterall,WA
影响因子：
56.9
作者：
RAGSDALE, DS;MCPHEE, JC;CATTERALL, WA
通讯作者：
CATTERALL, WA