Maitotoxin-induced membrane current in neuroblastoma cells.
Maitotoxin-induced membrane current in neuroblastoma cells.
复制标题
麦托毒素诱导神经母细胞瘤细胞膜电流。
DOI：
10.1016/0006-8993(87)91200-5
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发表时间：
1987
期刊：
影响因子：
2.9
通讯作者：
Narahashi,T
中科院分区：
文献类型：
--
作者：
Yoshii,M;Tsunoo,A;Kuroda,Y;Wu,CH;Narahashi,T
毛霉毒素(MTX)是从有毒的甲藻毒素冈比亚中分离出来的一种强效海洋毒素。我们用培养的神经母细胞瘤细胞(N1E-115)研究了MTX激活钙通道的可能性。甲氨蝶呤(10 ng/ml)可引起膜的去极化，这种去极化作用可被外源性介质中的钙离子清除所阻止。在电压钳条件下，以50 mM Ba2+为载流子，通过钙通道记录膜电流。应用甲氨蝶呤(1 ng/ml)后，维持膜在−90 mV所需的内向电流逐渐增加。随后，在−为30 mV时，通过I型钙通道的瞬时内向电流逐渐减小，最终被取消。通过II型钙通道的Ba2+内向电流也有类似的趋势，记录在+10 mV。钙通道阻滞剂维拉帕米(10 0μM)和La3+(1 NM)可拮抗MTX的作用。高浓度的维拉帕米(500μM)持续阻断这两种钙通道。在维拉帕米被清除后，当钙通道仍然被阻断时，MTX(1 ng/ml)产生一种稳态电流。甲氨蝶呤诱导电流表现出内向整流特性，其反向电位约为−30 mV。结果表明，MTX诱导的电流不流经钙通道。因此，MTX可能会在膜上形成一个孔，其药理特性类似于钙通道。
Maitotoxin (MTX) is a potent marine toxin isolated from the toxic dinoflagellate,Gambierdiscus toxicus. We have examined the possibility of MTX activating calcium channels using cultured neuroblastoma cells (N1E-115). MTX (10 ng/ml) produced a depolarization of the membrane, which was prevented by the removal of Ca2+from the external medium. Under voltage clamp conditions, membrane currents were recorded with 50 mM Ba2+as a charge carrier through calcium channels. After application of MTX (1 ng/ml), an inward current necessary to hold the membrane at −90 mV increased progressively. This was followed by a gradual decrease of the transient inward Ba2+current through type I calcium channels recorded at −30 mV which was eventually abolished. A similar tendency was observed in the long-lasting inward Ba2+current through type II calcium channels, which was recorded at +10 mV. The MTX action was antagonized by calcium channel blockers such as verapamil (100 μM) and La3+(1 nM). A high concentration of verapamil (500 μM) blocked both types of calcium channels persistently. After washout of verapamil but while the calcium channels were still blocked, MTX (1 ng/ml) induced a steady-state current. The MTX-induced current showed an inward-rectifying property with a reversal potential of approximately −30 mV. The results suggest that the MTX-induced current does not flow through calcium channels. Thus, MTX may create a pore in the membrane with pharmacological properties similar to those of calcium channels.