Pharmacologically and functionally distinct calcium currents of stomatogastric neurons.
Pharmacologically and functionally distinct calcium currents of stomatogastric neurons.
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DOI：
10.1152/jn.1998.79.4.2070
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发表时间：
1998-04
影响因子：
2.5
通讯作者：
L. Hurley;K. Graubard
中科院分区：
文献类型：
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作者：
L. Hurley;K. Graubard
先前的研究表明，在口胃神经元的不同区域存在不同类型的钙通道。我们试图从药理学上分离这些钙通道类型。我们使用来自口胃神经元不同区域的两种不同制剂来筛选一系列选择性钙通道阻滞剂。两种制剂分别为分离培养细胞体，直接测定钙电流；分离神经肌肉接点，间接测定突触前钙内流。选择性阻滞剂是两种不同的二氢吡啶，omega-Agatoxin IVA和omega- concontoxin GVIA。培养的细胞体具有高阈值钙电流和钙激活的外向电流，与完整的神经元相似。钙电流有瞬态成分和维持成分，但两者具有相同的激活和失活的电压依赖性。在>/=10微米时，二氢吡啶阻断了高阈值钙电流和钙激活的外向电流。纳摩尔剂量的ω - agatoxin IVA不能阻断钙电流，但微摩尔剂量可以。omega- concontoxin GVIA没有阻断任何电流。相比之下，在神经肌肉连接处，二氢吡啶仅适度降低突触后电位的幅度，而低至64 nM的omega-Agatoxin IVA几乎完全降低了突触后电位的幅度。这些影响是突触前的。omega- concontoxin GVIA未改变突触后电位振幅。两种分离制剂的不同药理学特征表明，口胃神经元中至少存在两种不同类型的钙通道，并且ω - agatoxin IVA和二氢吡啶可以用于药理学区分它们。
Previous studies have suggested the presence of different types of calcium channels in different regions of stomatogastric neurons. We sought to pharmacologically separate these calcium channel types. We used two different preparations from different regions of stomatogastric neurons to screen a range of selective calcium channel blockers. The two preparations were isolated cell bodies in culture, in which calcium current was measured directly, and isolated neuromuscular junction, in which synaptic transmission was the indirect assay for presynaptic calcium influx. The selective blockers were two different dihydropyridines, omega-Agatoxin IVA, and omega-Conotoxin GVIA. Cultured cell bodies possessed both high-threshold calcium current and calcium-activated outward current, similar to intact neurons. The calcium current had transient and maintained components, but both components had the same voltage dependence of activation and inactivation. Dihydropyridines at >/=10 microM blocked both high-threshold calcium current and calcium-activated outward current. Nanomolar doses of omega-Agatoxin IVA did not block calcium current, but micromolar doses did. omega-Conotoxin GVIA did not block either current. In contrast, at the neuromuscular junction, dihydropyridines reduced the amplitude of postsynaptic potentials by only a modest amount, whereas omega-Agatoxin IVA at doses as low as 64 nM reduced the amplitude of postsynaptic potentials almost entirely. These effects were presynaptic. omega-Conotoxin GVIA did not change the amplitude of postsynaptic potentials. The different pharmacological profiles of the two isolated preparations suggest that there are at least two different types of calcium channel in stomatogastric neurons and that omega-Agatoxin IVA and dihydropridines can be used to pharmacologically distinguish them.