Wales Heart Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, United Kingdom.
Sci Rep. 2016 Oct 5;6:34452. doi: 10.1038/srep34452.
The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel's selectivity filter and its ability to alter gating, with most studies involving prokaryotic K channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K channels makes unambiguous interpretation of data from single channel recordings difficult. In this study, the large K conductance of the RyR2 channel permits direct observation of blocking events as distinct subconductance states and for the first time demonstrates the differential effects of blocker molecules on channel gating. This experimental platform provides valuable insights into mechanisms of blocker-induced modulation of ion channel gating.
离子通过膜通道的流动是由门精确调节的。这些元件的结构和功能已经被广泛研究，揭示了门控的机制。最近的研究集中在通道选择性过滤器中离子的占据及其改变门控的能力，大多数研究涉及原核 K 通道。一些研究使用大的季铵阻断剂分子来研究改变离子通量对门控的影响。然而，在 K 通道中，没有明显区别于关闭事件的阻断事件，使得从单通道记录中获得的数据的明确解释变得困难。在这项研究中，RyR2 通道的大电导允许直接观察到阻断事件作为不同的次电导状态，并首次证明了阻断剂分子对通道门控的差异影响。这个实验平台为了解阻断剂诱导离子通道门控调制的机制提供了有价值的见解。
