Direct activation of the ATP sensitive potassium channel by oxygen free radicals in guinea pig ventricular cells: Its potentiation by MgADP
Direct activation of the ATP sensitive potassium channel by oxygen free radicals in guinea pig ventricular cells: Its potentiation by MgADP
复制标题
DOI：
10.1006/jmcc.1996.0179
复制
发表时间：
1996-09-01
影响因子：
5
通讯作者：
Tanaka, H
中科院分区：
文献类型：
--
作者：
Ichinari, K;Kakei, M;Tanaka, H
应用膜片钳技术，在由内而外的膜片上观察了过氧化氢（H_2O_2）对豚鼠心室肌细胞5 ′-三磷酸腺苷敏感钾（K-ATP（+））通道活性的影响。在0.3 mM ATP存在下，浓度为5 mM但不是1 mM的H2 O2增加K-ATP（+）通道活性。10 μ M ADP与0.3 mM ATP的存在下，导致激活的K+（ATP）通道由1 mM H2 O2。这种增强ADP对H_2O_2诱导的K-ATP（+）通道的激活作用依赖于Mg-ATP的存在。通道激活是由于开放状态概率的增加，与单通道电导的变化或突发式开放期间的平均开放和关闭时间无关。通道活性与ATP浓度之间的关系可用Hill方程拟合，其Kill系数为2，在10 μ M ADP存在下，在85 μ M ATP下的半数最大抑制。曲线通过1 mM H2 O2以非平行方式移动到更高的ATP浓度。含有几个通道的膜补丁的开放状态概率的分析表明，过氧化氢激活的个别通道在不同程度上。结论：H_2O_2通过降低ATP敏感性直接激活K-ATP（+）通道。ADP的存在增强了这种效应。(C)1996年学术出版社
The effects of hydrogen peroxide (H2O2) on the activity of adenosine 5'-triphosphate-sensitive potassium (K-ATP(+)) channels in ventricular cells isolated from guinea-pig hearts were investigated in inside-out membrane patches using the patch-clamp technique. H2O2 at concentrations of 5 mM but not 1 mM increased K-ATP(+) channel activity in the presence of 0.3 mM ATP. The presence of 10 mu M ADP together with 0.3 mM ATP led to activation of the K+(ATP) channel by 1 mM H2O2. This potentiation of the H2O2-induced activation of the K-ATP(+) channel by ADP depended on the presence of Mg-ATP. Channel activation was due to an increase in the open-state probability and was not associated with a change in the single-channel conductance or the mean open and closed times during burst-like openings. The relationship between channel activity and ATP concentration could be fitted by the Hill equation with a Kill coefficient of 2 and the half maximal inhibition at 85 mu M ATP in the presence of 10 mu M ADP. The curve was shifted to higher ATP concentrations in a non-parallel manner by 1 mM H2O2. Analysis of open-state probability for membrane patches containing several channels indicated that H2O2 activated the individual channels to a differing extent. It is concluded that H2O2 activates the K-ATP(+) channel directly by decreasing the sensitivity to ATP. This effect was potentiated by the presence of ADP. (C) 1996 Academic Press Limited