Calcium-permeable channels in rat hepatoma cells are activated by extracellular nucleotides.

Calcium-permeable channels in rat hepatoma cells are activated by extracellular nucleotides.
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大鼠肝癌细胞中的钙渗透通道被细胞外核苷酸激活。

DOI:
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发表时间:
1991
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通讯作者:
Canhui Li
Canhui Li
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文献类型:
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作者:
C. Bear;Canhui Li

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已知细胞外ATP引起大鼠肝细胞摄取Ca 2+。允许Ca 2+流入的特定途径尚未确定。在本研究中,我们研究了ATP诱发的大鼠肝癌细胞单层45 Ca ~(2+)摄取的特性,然后使用膜片钳电生理学来确定可能解释这种摄取的通道。结果表明,ATP刺激的45 Ca 2+摄取发生作为P2-嘌呤能受体相互作用的结果,因为摄取被抑制活性蓝(100 μ M),这种类型的受体的阻断剂。此外,其他腺嘌呤核苷酸刺激~(45)Ca ~(2+)摄取的能力与P2-嘌呤受体结合的选择性序列有关。ATP刺激的45 Ca 2+摄取主要通过电导孔发生,因为它被抑制70%后,使用K+离子载体缬氨霉素的膜电位耗散。钙通道阻滞剂硝苯地平和维拉帕米不能抑制~(45)Ca ~(2+)的摄取,但钆(GdCl_3)是一种有效的阻滞剂。在细胞贴附膜片钳实验中,在32次试验中的18次中,在浴中加入ATP(100 μ M)激活了单一类型的通道。ATP激活通道的电流-电压关系与本实验室先前表征为钙渗透性阳离子非选择性通道的牵张激活通道的电流-电压关系相同[Am. J.Physiol.258(Cell Physiol.27):C421-C428,1990]。有几条证据表明,这种阳离子非选择性通道可以解释ATP刺激的45 Ca 2+摄取。(250字处删节)
Extracellular ATP is known to cause uptake of Ca2+ by rat liver cells. The specific pathway permitting influx of Ca2+ has not yet been identified. In the present investigations, we studied the properties of ATP-evoked 45Ca2+ uptake in rat hepatoma cell monolayers and then used patch-clamp electrophysiology to identify the channel that may account for this uptake. The results suggest that ATP-stimulated 45Ca2+ uptake occurs as a result of P2-purinergic receptor interaction because uptake was inhibited by Reactive Blue (100 microM), a blocker of this type of receptor. Furthermore, the ability of other adenine nucleotides to stimulate 45Ca2+ uptake was related to the selectivity sequence for binding to the P2-purinergic receptor. ATP-stimulated 45Ca2+ uptake occurs primarily through a conductance pore since it was inhibited by 70% upon dissipation of the membrane potential using the K+ ionophore valinomycin. The calcium channel blockers nifedipine and verapamil failed to inhibit 45Ca2+ uptake, but gadolinium (GdCl3) was an effective blocker. In cell-attached patch-clamp experiments, a single type of channel was activated with ATP (100 microM) addition to the bath in 18 of 32 trials. The current-voltage relationship of the ATP-activated channel is identical to that of the stretch-activated channel previously characterized in this laboratory as a calcium-permeable cation-nonselective channel [Am. J. Physiol. 258 (Cell Physiol. 27): C421-C428, 1990]. There are several lines of evidence which suggest that this cation-nonselective channel may account for ATP-stimulated 45Ca2+ uptake.(ABSTRACT TRUNCATED AT 250 WORDS)