Ion Channel Biophysics Group, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA.
Prog Biophys Mol Biol. 2013 Jan;111(1):1-7. doi: 10.1016/j.pbiomolbio.2012.08.005. Epub 2012 Aug 17.
The rapidly activating, voltage gated Na(+) current, INa, has recently been measured in mammalian nonmyelinated axons. Those results have been incorporated in simulations of the action potential, results that demonstrate a significant separation in time during the spike between INa and the repolarizing K(+) current, IK. The original Hodgkin and Huxley (1952) model of Na(+) channel gating, m(3)h, where m and h are channel activation and inactivation, respectively, has been used in this analysis. This model was originally developed for invertebrate nonmyelinated axons, squid giant axons in particular. The model has not survived challenges based on results from invertebrate preparations using a double-step voltage clamp protocol and measurements of gating currents, results that demonstrate a kinetic link between activation and inactivation leading to a delayed onset of inactivation following a voltage step. These processes are independent of each other in the Hodgkin and Huxley (1952) model. Application of the double-step protocol to the m(3)h model for mammalian INa results reveals a surprising prediction, an apparent delay in onset of inactivation even though activation and inactivation are uncoupled in the model. Other results, most notably gating currents, will be required to demonstrate such a link, if indeed it exists for mammalian Na(+) channels. The information obtained will be significant in determining the way in which the Na(+) channel is sequestered away from its open state during repolarization, thereby allowing for a separation in time between INa and IK during a spike, an energetically efficient mechanism of neuronal signaling in the mammalian brain.
快速激活、电压门控的 Na(+)电流 INa 最近在哺乳动物无髓轴突中进行了测量。这些结果已被纳入动作电位的模拟中，结果表明在 spike 期间 INa 和复极化 K(+)电流 IK 之间存在明显的时间分离。原始的 Hodgkin 和 Huxley（1952）Na(+)通道门控模型 m(3)h，其中 m 和 h 分别代表通道的激活和失活，已用于此分析。该模型最初是为无脊椎动物无髓轴突开发的，特别是鱿鱼巨轴突。该模型最初是为无脊椎动物制剂的结果而开发的，这些结果使用了两步电压钳协议和门控电流测量，结果表明激活和失活之间存在动力学联系，导致失活在电压阶跃后延迟开始。在 Hodgkin 和 Huxley（1952）模型中，这些过程彼此独立。将两步协议应用于哺乳动物 INa 的 m(3)h 模型会产生一个惊人的预测，即失活的起始出现明显延迟，尽管在模型中激活和失活是解耦的。如果哺乳动物 Na(+)通道确实存在这种联系，其他结果，尤其是门控电流，将需要证明这一点。获得的信息对于确定 Na(+)通道在复极化期间如何远离其开放状态被隔离将是重要的，从而在 spike 期间 INa 和 IK 之间实现时间分离，这是哺乳动物大脑中神经元信号传递的一种节能机制。
