FUNCTIONAL SIGNIFICANCE OF SODIUM CHANNELS IN PANCREATIC BETA-CELL MEMBRANES
FUNCTIONAL SIGNIFICANCE OF SODIUM CHANNELS IN PANCREATIC BETA-CELL MEMBRANES
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DOI：
10.1113/jphysiol.1977.sp011817
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发表时间：
1977-01-01
影响因子：
5.5
通讯作者：
TAYLOR, P
中科院分区：
文献类型：
--
作者：
DONATSCH, P;LOWE, DA;TAYLOR, P
胰腺Na通道的存在及其功能意义。通过研究植物生物碱缬草碱对大鼠离体朗格汉胰岛胰岛素的时间释放的影响，探讨了胰岛素对大鼠离体朗格汉胰岛细胞膜的影响。Veratridine（100 .亩）M)引起胰岛素释放持续增加3倍，而3 .mu几乎完全抑制了胰岛素释放。M河豚毒素。TTX的作用可迅速逆转。同时存在100亩。心得安，100亩。10 μ M phenoxybenzamine。阿托品对100 .mu的反应幅度没有改变。M缬草碱，表明缬草碱对。β。-细胞是直接的，而不是通过胰岛内神经末梢的神经递质释放介导的。在静态培养中，孤立的胰岛对钙的吸收增加了近3倍。M藜芦定。这种增加被同时存在的3 .mu完全抑制。M TTX。胆碱替代钠（Na外）导致胰岛素释放短暂增加4倍，这与细胞外空间45Ca摄取增加相似幅度有关。随后暴露在100亩的小岛上。M缬曲啶仍能诱发胰岛素释放，但仅达到正常培养基中暴露于缬曲啶的胰岛分泌胰岛素的32% [Na]。在培养液中加入2.5 mM的CoCl2，对缬草碱介导的胰岛素释放有62.5%的抑制作用。在无ca培养基中添加1mm EGTA[乙二醇双β]。-氨基乙醚N，N，N‘，N’ -四乙酸]100 .亩。缬曲定诱发的胰岛素释放量与正常情况下相同，且具有相似的时间关系[Ca]。在暴露于1mm瓦巴因后的15分钟内，胰岛素释放量增加了2倍，这与[Ca]完全无关。随后的卡因诱发释放越来越依赖于[Ca]。河豚毒素（3 .亩）M)抑制16.7 mM d -葡萄糖诱导的第一期胰岛素释放37%，第二期胰岛素释放20%。钠离子和钙离子似乎都能够通过β中打开的钠离子通道进入。veratridine -细胞膜。由缬草碱介导的PNa+ [Na通透性]的增加引起的[Na]i[内Na]的增加，使。β去极化。-细胞膜，随后打开电压敏感的，Co2+可阻塞的通道，以便额外的Ca进入。[Na]i的增加也通过改变细胞内钙固存机制的平衡而增加[Ca]i。TTX对葡萄糖介导的胰岛素释放虽小但显著减少，这表明葡萄糖对Na通道的作用相当微弱，而对电压依赖性Co2+可阻断的Ca通道的作用更为明显。
The existence and functional significance of Na channels in pancreatic .beta.-cell membranes were investigated by studying the effects of the plant alkaloid veratridine on the temporal release of insulin from perfused isolated rat islets of Langerhans. Veratridine (100 .mu.M) evoked a sustained 3-fold increase in insulin release which was almost completely inhibited by 3 .mu.M tetrodotoxin (TTX). TTX action was rapidly reversible. The simultaneous presence of 100 .mu.M propranolol, 100 .mu.M phenoxybenzamine and 10 .mu.M atropine did not alter the magnitude of the response to 100 .mu.M veratridine, indicating that the action of veratridine on the .beta.-cells was direct and was not mediated via the release of neurotransmitters from nerve endings within the islets. 45Ca uptake by isolated islets in static incubation was increased almost 3-fold by 100 .mu.M veratridine. This increase was completely inhibited by the simultaneous presence of 3 .mu.M TTX. Replacement of Nao [outside Na] by choline caused a transient 4-fold increase in insulin release which was associated with an increase in the uptake of 45Ca from the extracellular space of similar magnitude. Subsequent exposure of islets to 100 .mu.M veratridine still evoked some insulin release but this only achieved 32% of that secreted by islets exposed to veratridine in medium of normal [Na]o. Addition of 2.5 mM CoCl2 to the medium caused a 62.5% inhibition of veratridine-mediated insulin release. In Ca-free medium supplemented with 1 mM EGTA [ethylene glycol bis (.beta.-aminoethyl ether N,N,N'',N''- tetraacetic acid] 100 .mu.M veratridine evoked insulin release of equal magnitude and of similar temporal relationship to that obtained in the presence of normal [Ca]o. A 2-fold increase in insulin release that occurred in the 15 min period immediately following exposure to 1 mM ouabain was completely independent of [Ca]o. Subsequent ouabain-evoked release became increasingly dependent on [Ca]o. Tetrodotoxin (3 .mu.M) inhibited the 1st phase of insulin release evoked by 16.7 mM D-glucose by 37% and the 2nd phase by 20%. Both Na and Ca appear capable of entering through Na channels opened in the .beta.-cell membrane by veratridine. The increase in [Na]i [inside Na], resulting from the veratridine mediated increase in PNa+ [Na permeability], depolarizes the .beta.-cell membrane with a consequent opening of voltage-sensitive, Co2+-blockable channels for additional Ca entry. An increase in [Na]i also increases [Ca]i by altering the equilibria of intracellular Ca-sequestering mechanisms. The small but significant reduction of glucose-mediated insulin release by TTX indicates that glucose has a rather weak action on the Na channel and a more pronounced effect on the voltage-dependent Co2+-blockable Ca channel.