A HERG-like K+ channel in rat F-11 DRG cell line: Pharmacological identification and biophysical characterization
A HERG-like K+ channel in rat F-11 DRG cell line: Pharmacological identification and biophysical characterization
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DOI：
10.1113/jphysiol.1996.sp021661
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发表时间：
1996-10-01
影响因子：
5.5
通讯作者：
Wanke, E
中科院分区：
文献类型：
--
作者：
Faravelli, L;Arcangeli, A;Wanke, E
1.在大鼠背根神经节（DRG）×小鼠神经母细胞瘤杂交细胞系（F-11）中，通过药物和生物物理处理，研究了神经母细胞瘤细胞中存在的K+内向整流电流（I-IR）与人类ether-a-go-go-related基因（HERG）编码的电流I-HERG和快速激活复极化电流I-K（r）之间的关系. I-IR与I-K（r）具有相同的药理学特征，包括对抗肿瘤药物E4031和WAY-123，398的敏感性，同时以与I-HERG 3相似的方式对Cs+、Ba 2+和La 3+产生反应。I-IR的电压依赖性门控特性与I-K（r）和I-HERG相似，但I-IR外向电流可忽略不计.在缺乏二价阳离子的高K+细胞外溶液中，I-IR失活动力学被去除，导致在超极化中明显激活的持久电流，电导显著增加（2.7倍），如从-120 mV的瞬时线性电流-电压关系记录的。Ca 2+的重新加入使通道恢复了原来的关闭状态，而Mg 2+的重新加入则使峰电流降低.本文所述的I-IR、心脏I-K（r）和I-HERG可以通过独特的动力学模型成功预测，其中激活/失活门的电压依赖性被适当地电压移位。总的来说，I-IR似乎是HERG型电流在神经元谱系的哺乳动物细胞中组成性表达和运作的第一个例子。
1. The relationships between the K+ inward rectifier current present in neuroblastoma cells (I-IR) and the current encoded by the human ether-a-go-go-related gene (HERG), I-HERG, and the rapidly activating repolarizing cardiac current I-K(r), were investigated in a rat dorsal root ganglion (DRG) x mouse neuroblastoma hybrid cell line (F-11) using pharmacological and biophysical treatments.2. I-IR shared the pharmacological features described for I-K(r), including the sensitivity to the antiarrhythmic drugs E4031 and WAY-123,398, whilst responding to Cs+, Ba2+ and La3+ in a similar way to I-HERG3. The voltage-dependent gating properties of I-IR were similar to those of I-K(r) and I-HERG, although I-IR outward currents were negligible in comparison.4. In high K+ extracellular solutions devoid of divalent cations, I-IR deactivation kinetics were removed resulting in long-lasting currents apparent:ly activated in hyperpolarization, with a marked (2.7-fold) increase in conductance, as recorded from the instantaneous linear current-voltage relationship at -120 mV. Re-addition of Ca2+ restored the original closure of the channel whereas re-addition of Mg2+ reduced the peak current.5. The I-IR described here, the heart I-K(r) and the I-HERG could be successfully predicted by a unique kinetic model where the voltage dependencies of the activation/inactivation gates were properly voltage shifted. On the whole, I-IR seems to be the first example of a HERG-type current constitutively expressed and operating in mammalian cells of the neuronal lineage.