Slow recovery from inactivation regulates the availability of voltage-dependent Na+ channels in hippocampal granule cells, hilar neurons and basket cells
Slow recovery from inactivation regulates the availability of voltage-dependent Na+ channels in hippocampal granule cells, hilar neurons and basket cells
复制标题
DOI：
10.1111/j.1469-7793.2001.0385f.x
复制
发表时间：
2001-04-15
影响因子：
5.5
通讯作者：
Beck, H
中科院分区：
文献类型：
--
作者：
Ellerkmann, RK;Riazanski, V;Beck, H
1.理解中枢神经系统功能的基础是单个神经元如何将多个突触输入整合成由携带编码为尖峰频率的信息的动作电位序列组成的输出的问题。神经元Naf通道激活的可用性对于该过程是至关重要的，并且通过快速和缓慢失活过程来调节。在这里，我们详细研究了海马神经元的慢失活过程。在室温下，通过延长（10-300 s）阶跃去极化至-10 mV诱导缓慢失活。在分离的海马齿状颗粒细胞（DGCs），从这种失活的恢复是双指数的，与时间常数的两个阶段的缓慢失活tau（慢，1）和tau（慢，2）的范围从10秒和20至50秒，分别。（τ慢，1）和τ（慢，2）两者都通过形式为τ（t）= a（t/a）（B）的幂律函数与先前去极化的持续时间相关，其中t是去极化的持续时间，a是恒定的动力学设定点，而B是缩放能力。该分析得出大鼠中tau（慢，1）的a = 0.034 s和B = 0.62，tau（慢，2）的a = 24 s和B = 0.30。当使用一系列不同频率（50、100、200 Hz）的动作电位样去极化来诱导失活时，在tau（慢，1）和tau（慢，2）的频率之间发现了类似的关系（tau（慢，1）的a = 0.58 s，B = 0.39; tau（慢，2）的a = 3.77 s，B = 0.42）。利用大鼠海马脑片的有核斑块，ave已经解决了慢失活中可能的细胞特异性差异。在快速尖峰的篮状细胞中，可以发现类似的比例关系（a = 3.54 s和B = 0.39），如在来自DGC的有核斑（a = 2.3 s和B = 0.48）和非快速尖峰的门神经元（a = 2.57 s和B = 0.49）中。同样，人类和大鼠颗粒细胞的比较表明，从失活超慢恢复的特性在物种间是保守的。在这两个物种中，超慢恢复是双指数的，tau（慢，1）和tau（慢，2）都与去极化持续时间t相关，对于tau（慢，1），a = 0.63 s和B = 0.44;对于人类受试者，tau（慢，2），a = 25 s和B = 0.37。总之，我们详细描述了Naf通道的生物物理特性如何导致钠通道的可用性和膜电位或动作电位频率之间复杂的相互关系，这可能有助于在不同类型的海马神经元中以秒至分钟的时间尺度进行时间整合。
1. Fundamental to the understanding of CNS function is the question of how individual neurons integrate multiple synaptic inputs into an output consisting of a sequence of action potentials carrying information coded as spike frequency. The availability for activation of neuronal Naf channels is critical for this process and is regulated both by fast and slow inactivation processes. Here, we have investigated slow inactivation processes in detail in hippocampal neurons.2. Slow inactivation was induced by prolonged (10-300 s ) step depolarisations to -10 mV at room temperature. In isolated hippocampal dentate granule cells (DGCs), recovery from this inactivation was biexponential, with time constants for the two phases of slow inactivation tau (slow,1) and tau (slow,2) ranging from to 10 s and 20 to 50 s, respectively. Both (tau slow,1) and tau (slow,2) were related to the duration of prior depolarisation by a power law function of the form tau (t) = a(t/a)(b), where t is the duration of the depolarisation, a is a constant kinetic setpoint and b is a scaling power. This analysis yielded values of a = 0.034 s and b = 0.62 for tau (slow,1) and a = 24 s and b = 0.30 for tau (slow,2) in the rat.3. When a train of action potential-like depolarisations of different frequencies (50, 100, 200 Hz) was used to induce inactivation, a similar relationship was found between the frequency of both tau (slow,1) and tau (slow,2) (a = 0.58 s, b = 0.39 for tau (slow,1) and a = 3.77 s and b = 0.42 for tau (slow,2)).4. Using nucleated patches from rat hippocampal slices, ave have addressed possible cell specific differences in slow inactivation. In fast-spiking basket cells a similar scaling relationship can be found (a = 3.54 s and b = 0.39) as in nucleated patches from DGCs (a = 2.3 s and b = 0.48) and non-fast-spiking hilar neurons (a = 2.57 s and b = 0.49).5. Likewise, comparison of human and rat granule cells showed that properties of ultra-slow recovery from inactivation are conserved across species. In both species ultra-slow recovery was biexponential with both tau (slow,1) and tau (slow,2) being related to the duration of depolarisation t, with a = 0.63 s and b = 0.44 for tau (slow,1) and a = 25 s and b = 0.37 for tau (slow,2) for the human subject.6. In summary, we describe in detail how the biophysical properties of Naf channels result in a complex interrelationship between availability of sodium channels and membrane potential or action potential frequency that may contribute to temporal integration on a time scale of seconds to minutes in different types of hippocampal neurons.