Hess P, Tsien R W
Nature. 1984;309(5967):453-6. doi: 10.1038/309453a0.
Calcium channels carry out vital functions in a wide variety of excitable cells but they also face special challenges. In the medium outside the channel, Ca2+ ions are vastly outnumbered by other ions. Thus, the calcium channel must be extremely selective if it is to allow Ca2+ influx rather than a general cation influx. In fact, calcium channels show a much greater selectivity for Ca2+ than sodium channels do for Na+ despite the high flux that open Ca channels can support. Relatively little is known about the mechanism of ion permeation through Ca channels. Earlier models assumed ion independence or single-ion occupancy. Here we present evidence for a novel hypothesis of ion movement through Ca channels, based on measurements of Ca channel activity at the level of single cells or single channels. Our results indicate that under physiological conditions, the channel is occupied almost continually by one or more Ca2+ ions which, by electrostatic repulsion, guard the channel against permeation by other ions. On the other hand, repulsion between Ca2+ ions allows high throughput rates and tends to prevent saturation with calcium.
钙通道在多种可兴奋细胞中发挥着至关重要的作用，但它们也面临着特殊的挑战。在通道外部的介质中，Ca2+离子的数量远远少于其他离子。因此，如果钙通道要允许Ca2+内流而不是一般阳离子内流，就必须具有极高的选择性。事实上，尽管开放的钙通道能够支持高通量，但钙通道对Ca2+的选择性远高于钠通道对Na+的选择性。关于离子通过钙通道的渗透机制，人们所知相对较少。早期模型假定离子独立或单离子占据。在此，我们基于在单细胞或单通道水平上对钙通道活性的测量，提出了一种关于离子通过钙通道运动的新假说的证据。我们的结果表明，在生理条件下，通道几乎持续被一个或多个Ca2+离子占据，这些离子通过静电排斥作用，防止其他离子渗透通过通道。另一方面，Ca2+离子之间的排斥作用允许高通量速率，并倾向于防止钙饱和。
