Transient BK outward current enhances motoneurone firing rates during Drosophila larval locomotion
Transient BK outward current enhances motoneurone firing rates during Drosophila larval locomotion
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DOI：
10.1113/jp271323
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发表时间：
2015-11-15
影响因子：
5.5
通讯作者：
Duch, Carsten
中科院分区：
文献类型：
--
作者：
Kadas, Dimitrios;Ryglewski, Stefanie;Duch, Carsten
大量的电压门控离子通道，它们与辅助亚基的相互作用，以及它们的转录后修饰产生了巨大的神经元功能多样性。因此，一个关键的挑战是要了解的遗传基础和特定的离子电导神经元放电特性的行为背景下的精确功能。本研究确定慢波（slowpoke，简称慢波）是唯一介导果蝇幼虫爬行运动神经元快速激活、快速失活BK电流（I-CF）的通道。结合在体内膜片钳记录在幼虫爬行与药理学和有针对性的遗传操作揭示，I-CF的行为，特别是在运动神经元雕刻他们的放电模式，响应于一个给定的输入从中央模式生成（CPG）网络。首先，I-CF缩短运动神经元突触后去极化在有节奏的CPG驱动。第二，I-CF在动作电位的上升期被激活，并介导快速后超极化。因此，I-CF是运动过程中最大爆发内放电率所必需的，可能是通过允许从快钠通道失活和降低的钾通道激活中恢复。这与外向电导对抗兴奋性的普遍观点相反，但与多种类型脊椎动物神经元中瞬时BK和Kv 3通道功能的报道一致。因此，我们发现I-CF在与行为相关的突发模式期间特别增强放电率可能与所有大脑相关。
A large number of voltage-gated ion channels, their interactions with accessory subunits, and their post-transcriptional modifications generate an immense functional diversity of neurones. Therefore, a key challenge is to understand the genetic basis and precise function of specific ionic conductances for neuronal firing properties in the context of behaviour. The present study identifies slowpoke (slo) as exclusively mediating fast activating, fast inactivating BK current (I-CF) in larval Drosophila crawling motoneurones. Combining in vivo patch clamp recordings during larval crawling with pharmacology and targeted genetic manipulations reveals that I-CF acts specifically in motoneurones to sculpt their firing patterns in response to a given input from the central pattern generating (CPG) networks. First, I-CF curtails motoneurone postsynaptic depolarizations during rhythmical CPG drive. Second, I-CF is activated during the rising phase of the action potential and mediates a fast afterhyperpolarization. Consequently, I-CF is required for maximal intraburst firing rates during locomotion, probably by allowing recovery from inactivation of fast sodium channels and decreased potassium channel activation. This contrasts the common view that outward conductances oppose excitability but is in accordance with reports on transient BK and Kv3 channel function in multiple types of vertebrate neurones. Therefore, our finding that I-CF enhances firing rates specifically during bursting patterns relevant to behaviour is probably of relevance to all brains.