Inward rectification and voltage-dependent activation of HERG K channels

HERG K 通道的内向整流和电压依赖性激活

基本信息

批准号：
08670055
负责人：
ONO Kyoichi
金额：
$ 1.41万
依托单位：
AKITA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670055/
关键词：
HERG sinoatrial node delayd rectifier K current pacemaker activity IKr IKs 洞房結節 Caイオン

项目摘要

We have demonstrated that the conductance and kinetics of I_K in SA node cells closely resembled those of the rapidly activating component of I_K (I_<Kr>) which is coded by human eag-related gene (HERG), in terms of ion selectivity, gating parameters of activation, inward rectification of the steady-state IV relation, the single channel conductance, and selective blockage by class III antiarrythmic agents. The inward rectifying property was characterized by decrease of open probablity at positive potentials. Under the inside-out mode, the open probabilty did not increase even if the patch membrane was exposed to the solution containing on Mg^<2+> or Ca^<2+>, indicating that the inward rectification is not due to block by these cations but derived from the intirinsic gating of the I_<Kr> channels.When the external Ca^<2+> was removed, the decay of the tail current was markedly prolonged. The effect of external Ca^<2+> was voltage-and concentration-dependent. The results indicate that the gating of I_<Kr>, which has been believed to be an intrinsic voltage-dependent mechanism, might be caused by a time-and voltage-dependent block and unblock of the I_<Kr> channels by external Ca^<2+>.I_<Kr> is essential in maintaining the automaticity of rabbit SAN cells. To extend this hypothesis to other species, we made an attempt to isolate pacemaker cells from porcine hearts. The isolated cells exhibited spontaneous activity with beating rate of approximately 80 min-1 in normal Tyrode solution. It was found that the delayd rectifier K^+ current of porcine SAN cells consisted of the slowly activating delayd rectifier K + current, in contrast to I_<Kr> of rabbit. The different I_K might contribute to different heart rate among various species.

我们已经证明，在SA节点单元中I_K的电导和动力学与I_K（I_ <kr>）的快速激活成分的电导和动力学非常相似，该成分由人EAG相关基因（HERG）编码，就离子选择性而言激活的参数，稳态IV关系的内部整流，单个通道电导和通过III类抗乳腺剂的选择性阻塞。向内整流性质的特征是在正势下开放概率的降低。在内外模式下，即使将斑块膜暴露于Mg^<2+>或Ca^<2+>上的溶液中，开放的概率也不会增加这些阳离子，但源自I_ <kr>通道的固定门控。去除外部Ca^<2+>后，尾部电流的衰减显着延长。外部Ca^<2+>的作用是电压和浓度依赖性的。结果表明，I_ <kr>的门控被认为是固有的电压依赖性机制，可能是由于时间和电压依赖性的块和i_ <kr>通道的电压引起的。 <2+>。I_<kr>对于维持兔SAN细胞的自动化至关重要。为了将这一假设扩展到其他物种，我们试图将起搏器细胞与猪心分离。分离的细胞在正常的泰罗德溶液中表现出自发活性，击败速率约为80分钟1。发现猪SAN细胞的延迟整流器K^ +电流由兔子的I_ <kr>相比，由缓慢激活的延迟整流器K +电流组成。不同的I_K可能会导致各种物种之间的心率不同。