Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current.
Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current.
复制标题
Kv4.2电流与大鼠心脏瞬时外向电流之间的电生理和药理学对应关系。
DOI：
10.1016/s0008-6363(96)00221-0
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发表时间：
1997
影响因子：
10.8
通讯作者：
Snyders,DJ
中科院分区：
文献类型：
--
作者：
Yeola,SW;Snyders,DJ
目的：瞬时外向电流（ITO）在心脏动作电位的早期复极和全时程中起重要作用。从心脏组织中克隆的至少两个K+通道α亚基（Kv1.4和Kv4.2）编码快速失活通道。本研究的目的是确定在哺乳动物细胞中表达的Kv4.2的功能和药理学特性，特别是那些将区分两种异构体相比，nativeITO.Methods：Kv4.2和Kv1.4异构体在小鼠L-细胞系中稳定表达，并使用全细胞电压钳技术研究表达电流。失活的恢复速度很快（在−90 mV时τrecov= 160 ms），并且具有很强的电压依赖性。氟卡尼（10 μM）对Kv1.4电流的影响最小，但使Kv4.2峰电流降低53%，并增加了与开放通道阻滞一致的表观失活速率。奎尼丁（10-20 μM）降低了峰电流，并加快了两种亚型的表观灭活速率。结论：Kv4.2的功能特性，尤其是对氟卡尼的敏感性，与ITO在大鼠（和人）心肌细胞中的作用相似，优于Kv1.4。这些结果提供了必要的功能支持的假设，Kv4.2是一个主要的同种型cardiacITO，与独立的生化和分子证据表明，Kv4.2是很容易检测到大鼠心肌细胞一致。
Objective:The transient outward current (ITO) plays an important role in early repolarization and overall time course of the cardiac action potential. At least two K+channel α-subunits cloned from cardiac tissue (Kv1.4 and Kv4.2) encode rapidly inactivating channels. The goal of this study was to determine functional and pharmacological properties of Kv4.2 expressed in mammalian cells, especially those that would differentiate between both isoforms in comparison to nativeITO.Methods:Both Kv4.2 and Kv1.4 isoforms were stably expressed in mouse L-cell lines, and expressed currents were studied using whole-cell voltage clamp techniques.Results:The expressed Kv4.2 currents displayed fast inactivation with a half-inactivation potential of −41 mV. Recovery from inactivation was rapid (τrecov= 160 ms at −90 mV) and strongly voltage-dependent. Flecainide (10 μM) had minimal effects on Kv1.4 currents, but reduced Kv4.2 peak current by 53% and increased the apparent rate of inactivation consistent with open channel block. Quinidine (10–20 μM) reduced the peak current and accelerated the apparent rate of inactivation in both isoforms. The Kv4.2 current displayed use-dependent unblock in the presence of 4-AP.Conclusions:The functional properties of Kv4.2, especially the flecainide sensitivity, resemble those ofITOin rat (and human) myocytes better than those of Kv1.4. These results provide the necessary functional support for the hypothesis that Kv4.2 is a major isoform contributing to cardiacITO, consistent with independent biochemical and molecular evidence that indicates that Kv4.2 is readily detected in rat myocytes.