ADJACENT INTERVAL-ANALYSIS DISTINGUISHES AMONG GATING MECHANISMS FOR THE FAST CHLORIDE CHANNEL FROM RAT SKELETAL-MUSCLE
ADJACENT INTERVAL-ANALYSIS DISTINGUISHES AMONG GATING MECHANISMS FOR THE FAST CHLORIDE CHANNEL FROM RAT SKELETAL-MUSCLE
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DOI：
10.1113/jphysiol.1989.sp017549
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发表时间：
1989-03-01
影响因子：
5.5
通讯作者：
MAGLEBY, KL
中科院分区：
文献类型：
--
作者：
BLATZ, AL;MAGLEBY, KL
相邻的开放和关闭的时间间隔，获得与膜片钳技术从快速Cl-通道在组织培养的大鼠骨骼肌，进行了分析，以区分8个先前考虑的门控机制的通道，不同的状态之间的连接。研究结果表明，至少有两个开放状态是由独立的路径连接到不同的关闭状态;与快速开放组件相关的开放状态连接到一个关闭状态（或复合关闭状态）的有效寿命较长，和开放状态与缓慢开放组件连接到一个关闭状态（或复合关闭状态）的有效寿命较短。之前考虑的8个门控机制中有7个被拒绝，因为它们没有考虑到相邻开放和关闭间隔的持续时间之间的关系，当根据条件开放分布或条件平均开放间隔持续时间进行分析时。七个拒绝门控机制也没有考虑到观察到的相关性之间的间隔时间，相关系数进行分析时。因此，相邻间隔和校正分析提供了一种区分选通机制的方法。假设绝对速率理论，从一个一致动力学方案的速率常数推导出的自由能状态图表明，克服状态之间的有效跃迁势垒所需的自由能为11-15 kcal/mol，而连接的平衡状态之间的自由能差仅等于约0.5-1.5 kcal/mol。因此，如果状态之间的转变涉及弱键（氢键、货车德瓦尔斯键或盐桥）的断裂，那么每次转变后立即重新形成大约相同数量的键。
The durations of adjacent open and shut intervals, obtained with the patch-clamp technique from fast Cl- channels in tissue-cultured rat skeletal muscle, were analyzed to distinguish among eight previously considered gating mechanisms for the channel which differed in the connections among the states. The findings indicate that at least two open states are connected by independent pathways to different shut states; the open state associated with the fast open component is connected to a shut state (or compound shut state) of longer effective lifetime, and the open state associated with the slow open component is connected to a shut state (or compound shut state) of briefer effective lifetime. Seven of the eight previously considered gating mechanisms were rejected because they did not account for the observed relationships between the durations of adjacent open and shut intervals, when analysed in terms of either conditional open distributions or conditional mean open interval durations. The seven rejected gating mechanisms also did not account for the observed correlations between interval durations, when analysed in terms of correlation coefficients. Adjacent interval and correction analysis thus provided a means to distinguish among the gating mechanisms. A free energy state diagram derived, assuming absolute rate theory, from the rate constants for the one consistent kinetic scheme indicated that the free energy required to overcome the effective transition barriers between states was 11-15 kcal/mol, whereas the free energy difference between connected equilibrium states was equal to only about 0.5-1.5 kcal/mol. Thus, if transitions between states involve the breaking of weak bonds (hydrogen bonds, van der Waals bonds or salt bridges), then about the same equivalent number of bonds are reformed immediately ater each transition.