Crest M, Jacquet G, Gola M, Zerrouk H, Benslimane A, Rochat H, Mansuelle P, Martin-Eauclaire M F
Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique, Marseille, France.
J Biol Chem. 1992 Jan 25;267(3):1640-7.
A peptidyl inhibitor of the high conductance Ca(2+)-activated K+ channels (KCa) has been purified to homogeneity from the venom of the scorpion Androctonus mauretanicus mauretanicus. The peptide has been named kaliotoxin (KTX). It is a single 4-kDa polypeptide chain. Its complete amino acid sequence has been determined. KTX displays sequence homology with other scorpion-derived inhibitors of Ca(2+)-activated or voltage-gated K+ channels: 44% homology with charybdotoxin (CTX), 52% with noxiustoxin (NTX), and 44% with iberiotoxin (IbTX). Electrophysiological experiments performed in identified nerve cells from the mollusc Helix pomatia showed that KTX specifically suppressed the whole cell Ca(2+)-activated K+ current. KTX had no detectable effects on voltage-gated K+ current (delayed rectifier and fast transient A current) or on L-type Ca2+ currents. KTX interacts in a one-to-one way with KCa channels with a Kd of 20 nM. Single channel experiments were performed on high conductance KCa channels excised from the above Helix neurons and from rabbit coeliac ganglia sympathetic neurons. KTX acted exclusively at the outer face of the channel. KTX applied on excised outside-out KCa channels induced a transient period of fast-flicker block followed by a persistent channel blockade. The KTX-induced block was not voltage-dependent which suggests differences in the blockade of KCa channels by KTX and by CTX. Comparison of KTX and CTX sequences leads to the identification of a short amino acid sequence (26-33) which may be implicated in the toxin-channel interaction. KTX therefore appears to be a useful tool for elucidating the molecular pharmacology of the high conductance Ca(2+)-activated K+ channel.
一种高电导钙激活钾通道（KCa）的肽基抑制剂已从蝎毒Androctonus mauretanicus mauretanicus中纯化至同质。该肽被命名为卡利毒素（KTX）。它是一条单一的4 kDa多肽链。其完整的氨基酸序列已被确定。KTX与其他源自蝎子的钙激活或电压门控钾通道抑制剂具有序列同源性：与查氏毒素（CTX）有44%的同源性，与诺蝎毒素（NTX）有52%的同源性，与iberiotoxin（IbTX）有44%的同源性。在软体动物Helix pomatia的已鉴定神经细胞中进行的电生理实验表明，KTX特异性抑制全细胞钙激活钾电流。KTX对电压门控钾电流（延迟整流器和快速瞬态A电流）或L型钙电流没有可检测到的影响。KTX以一对一的方式与KCa通道相互作用，解离常数为20 nM。对从上述Helix神经元和兔腹腔神经节交感神经元中切除的高电导KCa通道进行了单通道实验。KTX仅作用于通道的外表面。将KTX应用于切除的外向型KCa通道会诱导一个快速闪烁阻断的短暂时期，随后是持续的通道阻断。KTX诱导的阻断不依赖电压，这表明KTX和CTX对KCa通道的阻断存在差异。比较KTX和CTX序列可确定一个短氨基酸序列（26 - 33），该序列可能与毒素 - 通道相互作用有关。因此，KTX似乎是阐明高电导钙激活钾通道分子药理学的有用工具。
