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慢,慢,快,快,慢:钙激活钾通道作为秀丽隐杆线虫行为的调节因子及驱虫药的靶点

SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics.

作者信息

Holden-Dye Lindy, O'Connor Vincent, Hopper Neil A, Walker Robert J, Harder Achim, Bull Kathryn, Guest Marcus

机构信息

School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK.

出版信息

Invert Neurosci. 2007 Dec;7(4):199-208. doi: 10.1007/s10158-007-0057-z. Epub 2007 Oct 26.

Abstract

Large-conductance calcium and voltage-activated potassium channels, termed SLO-1 (or BK), are pivotal players in the regulation of cell excitability across the animal phyla. Furthermore, emerging evidence indicates that these channels are key mediators of a number of neuroactive drugs, including the most recent new anthelmintic, the cyclo-octadepsipeptide emodepside. Detailed reviews of the structure, function and pharmacology of BK channels have recently been provided (Salkoff et al. in Nat Rev Neurosci 7:921-931, 2006; Ghatta et al. in Pharmacol Ther 110:103-116, 2006) and therefore these aspects will only briefly be covered here. The purpose of this review is to discuss how SLO-1 channels might function as regulators of neural transmission and network activity. In particular, we focus on the role of SLO-1 in the regulation of Caenorhabditis elegans behaviour and highlight the role of this channel as an effector for pleiotropic actions of neuroactive drugs, including emodepside. On the premise that C. elegans is a 'model nematode' with respect to many aspects of neural function, the intention is that this might inform a broader understanding of the role of these channels in the nematodes and their potential as novel anthelmintic targets.

摘要

大电导钙激活钾通道,称为SLO-1(或BK),是调控动物各门类细胞兴奋性的关键因子。此外,新出现的证据表明,这些通道是多种神经活性药物的关键介质,包括最新的新型驱虫药环八肽依莫地肽。最近已有关于BK通道结构、功能和药理学的详细综述(Salkoff等人,《自然神经科学综述》7:921 - 931,2006年;Ghatta等人,《药理学与治疗学》110:103 - 116,2006年),因此这里仅简要涵盖这些方面。本综述的目的是讨论SLO-1通道如何作为神经传递和网络活动的调节因子发挥作用。特别是,我们聚焦于SLO-1在秀丽隐杆线虫行为调节中的作用,并强调该通道作为神经活性药物(包括依莫地肽)多效性作用效应器的作用。鉴于秀丽隐杆线虫在神经功能的许多方面都是“模式线虫”,目的是这可能有助于更广泛地理解这些通道在该线虫中的作用及其作为新型驱虫靶点的潜力。

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