Wickenden A D, Tsushima R G, Losito V A, Kaprielian R, Backx P H
Department of Medicine and Centre for Cardiovascular Research, University of Toronto, The Toronto General Hospital, Toronto, Canada.
Cell Physiol Biochem. 1999;9(1):11-28. doi: 10.1159/000016299.
The aim of the present study was to compare the biophysical properties and Cd2+ sensitivity of Kv4.2 and Kv1.4 in Xenopus oocytes with those of native transient outward potassium currents in rat and rabbit ventricular myocytes. In Xenopus oocytes, Kv4.2 inactivated at hyperpolarized voltages (V(1/2)inact = -58.4 +/- 0.96 mV, n = 12) and recovered from inactivation rapidly (time constant = 224 +/- 23 ms, n = 3). Cd2+ induced large (approx. 30 mV with 500 microM Cd2+), concentration-dependent rightward shifts in Kv4.2 steady-state activation and inactivation. Kv1.4 inactivated over more depolarized voltages than Kv4.2 (V(1/2)inact = -49.3 +/- 1.4 mV, n = 12). Recovery from inactivation of Kv1.4 was dominated by a large slow component (time constant = 9,038 +/- 1,178 ms, n = 4). Cd2+ exerted only modest effects on Kv1.4 gating, with 500 microM Cd2+ shifting the voltage dependence of steady-state activation and inactivation by approximately 12 mV. We show that the biophysical properties and Cd2+ sensitivity of rat ventricular Ito resemble those of heterologously expressed Kv4.2. These findings support previous suggestions that Kv4.2 is an important molecular component of Ito in adult rat heart. In addition, our findings show that Ito in rabbit ventricular myocytes and Kv1.4-based currents in Xenopus oocytes share similar biophysical properties and sensitivity to Cd2+, suggesting that Kv1.4 may underlie Ito in rabbit ventricle. However, a number of discrepancies exist between the properties of native currents and their putative molecular counterparts, suggesting that additional proteins and/or modulatory factors may also play a role in determining the biophysical and pharmacological properties of these native currents.
本研究的目的是比较非洲爪蟾卵母细胞中Kv4.2和Kv1.4的生物物理特性及对Cd2+的敏感性与大鼠和兔心室肌细胞中天然瞬时外向钾电流的这些特性。在非洲爪蟾卵母细胞中，Kv4.2在超极化电压下失活（半数失活电压V(1/2)inact = -58.4±0.96 mV，n = 12），且从失活状态快速恢复（时间常数 = 224±23 ms，n = 3）。Cd2+导致Kv4.2稳态激活和失活出现大的（500 μM Cd2+时约为30 mV）、浓度依赖性的右移。Kv1.4比Kv4.2在更正的电压下失活（半数失活电压V(1/2)inact = -49.3±1.4 mV，n = 12）。Kv1.4从失活状态恢复主要由一个大的慢成分主导（时间常数 = 9,038±1,178 ms，n = 4）。Cd2+对Kv1.4门控仅产生适度影响，500 μM Cd2+使稳态激活和失活的电压依赖性右移约12 mV。我们表明，大鼠心室Ito的生物物理特性及对Cd2+的敏感性类似于异源表达的Kv4.2。这些发现支持了之前的观点，即Kv4.2是成年大鼠心脏中Ito的重要分子成分。此外，我们的发现表明，兔心室肌细胞中的Ito和非洲爪蟾卵母细胞中基于Kv1.4的电流具有相似的生物物理特性及对Cd2+的敏感性，提示Kv1.4可能是兔心室Ito的基础。然而，天然电流的特性与其假定的分子对应物之间存在一些差异，表明其他蛋白质和/或调节因子可能也在决定这些天然电流的生物物理和药理学特性中发挥作用。
