Dale N, Kuenzi F M
School of Biological and Medical Sciences, University of St Andrews, U.K.
Prog Neurobiol. 1997 Dec;53(6):729-56. doi: 10.1016/s0301-0082(97)00048-8.
The Xenopus embryo has been well studied and the circuitry underlying motor pattern generation largely elucidated. We have extended this analysis by determining the roles of individual voltage- and ligand-gated ion channels in controlling the motor pattern for swimming and two mechanisms that control rundown of this pattern. Xenopus embryo spinal neurons possess at least six classes of ion channel: a fast Na+ channel; a mixture of kinetically similar Ca2+ channels; a fast K+ channel; a slow K+ channel; a Na(+)-dependent K+ channel; and a slowly activating Ca2(+)-dependent K+ channel. The roles of the voltage-gated currents in determining neuronal firing properties and operation of the locomotor circuitry have been examined both pharmacologically and in realistic computer simulations. Model neurons fire repetitively in response to current injection. The Ca2+ current seems essential for repetitive firing. The fast K+ current appears mainly to control spike width, whereas the slow K+ current exerts a powerful influence on repetitive firing. These predictions from the model have been confirmed by the use of specific pharmacological blockers of the fast and slow K+ currents. Both the model network and the real spinal locomotor circuit appear to tolerate a wide variation in the relative strengths of the component synapses but are very sensitive to the magnitudes of the voltage-gated currents. In particular the slow K+ current, despite being a small component of the total outward current, plays a critical role in stabilizing the motor pattern. Like many other rhythmic motor patterns, swimming in the Xenopus embryo is episodic; it undergoes run-down and self-termination even in the absence of sensory inputs. The slow Ca2(+)-dependent K+ current appears to play a role in the self-termination of swimming. However, intrinsic modulation mediated by the release of ATP and production of adenosine in the extracellular space appears to be a very powerful determinant of run-down of the motor pattern.
非洲爪蟾胚胎已经得到了充分研究，运动模式产生的基础神经回路也基本阐明。我们通过确定单个电压门控和配体门控离子通道在控制游泳运动模式中的作用以及控制该模式衰退的两种机制，扩展了这一分析。非洲爪蟾胚胎脊髓神经元至少拥有六类离子通道：一种快速钠通道；动力学特性相似的钙通道混合物；一种快速钾通道；一种慢速钾通道；一种钠依赖性钾通道；以及一种缓慢激活的钙依赖性钾通道。通过药理学方法和逼真的计算机模拟，研究了电压门控电流在决定神经元放电特性和运动神经回路运作中的作用。模型神经元在电流注入时会重复放电。钙电流似乎对重复放电至关重要。快速钾电流似乎主要控制动作电位宽度，而慢速钾电流对重复放电有强大影响。通过使用快速和慢速钾电流的特异性药理学阻断剂，证实了该模型的这些预测。模型网络和实际的脊髓运动回路似乎都能容忍组成突触相对强度的广泛变化，但对电压门控电流的大小非常敏感。特别是慢速钾电流，尽管只是总外向电流的一小部分，但在稳定运动模式中起关键作用。与许多其他节律性运动模式一样，非洲爪蟾胚胎的游泳是间歇性的；即使在没有感觉输入的情况下，它也会经历衰退和自我终止。缓慢的钙依赖性钾电流似乎在游泳的自我终止中起作用。然而，由细胞外空间中ATP释放和腺苷产生介导的内在调节似乎是运动模式衰退的一个非常重要的决定因素。
