OMEGA-CONOTOXIN - DIRECT AND PERSISTENT BLOCKADE OF SPECIFIC TYPES OF CALCIUM CHANNELS IN NEURONS BUT NOT MUSCLE
OMEGA-CONOTOXIN - DIRECT AND PERSISTENT BLOCKADE OF SPECIFIC TYPES OF CALCIUM CHANNELS IN NEURONS BUT NOT MUSCLE
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DOI：
10.1073/pnas.84.12.4327
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发表时间：
1987-06-01
影响因子：
11.1
通讯作者：
YOSHIKAMI, D
中科院分区：
文献类型：
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作者：
MCCLESKEY, EW;FOX, AP;YOSHIKAMI, D
通过ω-阻断Ca 2+通道芋螺毒素GVIA是一种由27个氨基酸组成的多肽，来自于海洋蜗牛Conus geographus的毒液，用膜片钳记录全细胞和各种细胞类型的单位电流。在背根sanglion神经元，毒素产生持久的L-和N-型钙通道的阻滞，但只短暂抑制T-型通道。其作用似乎是神经元特异性的，因为它阻断脊椎动物的感觉、交感神经和海马神经元中的高阈值Ca 2+通道，但不阻断心脏、骨骼肌或平滑肌细胞中的高阈值Ca 2+通道。阻断通过毒素与与Ca 2+通道密切相关的外部位点的直接相互作用发生，而不明显涉及第二信使或依赖于通道门控。组织和通道类型特异性以及阻断的直接性和缓慢可逆性是有利于使用ω-的特征。芋螺毒素作为纯化特定神经元Ca 2+通道并确定其生理功能的工具。
Blockade of Ca2+ channels by .omega.-conotoxin GVIA, a 27 amino acid peptide from the venom of the marine snail Conus geographus, was investigated with patch-clamp recordings of whole-cell and unitary currents in a variety of cell tyeps. In dorsal root sanglion neurons, the toxin produces persistent block of L- and N-type Ca2+ channels but only transiently inhibits T-type channels. Its actions appear to be neuron-specific, since it blocks high-threshold Ca2+ channels in sensory, sympathetic, and hippocampal neurons of vertebrates but not in cardiac, skeletal, or smooth muscle cells. Block occurs through direct interaction of the toxin with an external site closely associated with the Ca2+ channel, without apparent involvement of a second messenger or dependence on channel gating. The tissue and channel-type specificity and the directness and slow reversibility of the block are features that favor use of .omega.-conotoxin as a tool for purifying particular neuronal Ca2+ channels and defining their phsyiological function.