Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic β-cells and HIT cells
Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic β-cells and HIT cells
复制标题
小鼠胰腺 β 细胞和 HIT 细胞中 ATP 敏感钾通道的腺嘌呤核苷酸调节的两个位点
DOI：
10.1007/bf00232910
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
D. Cook
中科院分区：
文献类型：
--
作者：
W. F. Hopkins;S. Fatherazi;B. Peter;B. Corkey;D. Cook
在培养的成年小鼠胰腺β细胞和HIT细胞中，研究了ATP抑制的钾通道（K(ATP)）。在没有ATP的情况下，ADP在低至10 μm和高至500 μm的浓度下打开K（ATP）通道，在小鼠β细胞膜斑块中，ADP在10 ~ 100 μm之间的激活最大。浓度大于500 μm时，ADP抑制K（ATP）通道，而浓度为10 μm时，ADP几乎消除了通道活性。HIT细胞通道对ADP有类似的双相反应，只是需要超过1 mm的ADP才能抑制。ADP的通道打开效应需要镁，而通道抑制不需要。使用含有肌酸磷酸激酶的肌酸/磷酸肌酸溶液来固定ATP和ADP浓度，我们发现具有相同ATP/ADP比率但绝对总核苷酸水平不同的溶液的K（ATP）通道活性存在显著差异。为了解释ATP-ADP竞争，我们提出了一种新的通道-核苷酸相互作用模型，其中两种ADP结合位点调节通道。一个位点特异性地结合MgADP并增加通道开放。另一个，前面描述的ATP位点，结合ATP或ADP并减少通道开放。该模型非常接近ADP浓度-响应曲线，当纳入β细胞膜电位模型时，预计在10和100 μm范围内增加ADP将非常有效地与毫摩尔水平的ATP竞争，从而使β细胞超极化。结果表明：(1)K（ATP）通道活性不能通过“ATP/ADP比率”很好地预测；(2)ADP是K（ATP）通道的合理调节剂，即使其游离细胞质浓度在生化研究表明的10-100 μm范围内。
SummaryATP-inhibited potassium channels (K(ATP)) were studied in excised, inside-out patches from cultured adult mouse pancreatic β-cells and HIT cells. In the absence of ATP, ADP opened K(ATP) channels at concentrations as low as 10 μm and as high as 500 μm, with maximal activation between 10 and 100 μm ADP in mouse β-cell membrane patches. At concentrations greater than 500 μm, ADP inhibited K(ATP) channels while 10 mm virtually abolished channel activity. HIT cell channels had a similar biphasic response to ADP except that more than 1 mm ADP was required for inhibition. The channel opening effect of ADP required magnesium while channel inhibition did not. Using creatine/creatine phosphate solutions with creatine phosphokinase to fix ATP and ADP concentrations, we found substantially different K(ATP)-channel activity with solutions having the same ATP/ADP ratio but different absolute total nucleotide levels. To account for ATP-ADP competition, we propose a new model of channel-nucleotide interactions with two kinds of ADP binding sites regulating the channel. One site specifically binds MgADP and increases channel opening. The other, the previously described ATP site, binds either ATP or ADP and decreases channel opening. This model very closely fits the ADP concentration-response curve and, when incorporated into a model of β-cell membrane potential, increasing ADP in the 10 and 100 μm range is predicted to compete very effectively with millimolar levels of ATP to hyperpolarize β-cells.The results suggest that (i) K(ATP)-channel activity is not well predicted by the “ATP/ADP ratio,” and (ii) ADP is a plausible regulator of K(ATP) channels even if its free cytoplasmic concentration is in the 10–100 μm range as suggested by biochemical studies.
登录
查看更多内容
DOI：
10.1073/pnas.83.18.7119
发表时间：
1986-09-01
影响因子：
11.1
作者：
MISLER, S;FALKE, LC;MCDANIEL, ML
通讯作者：
MCDANIEL, ML
离体大鼠朗格汉斯岛能量水平与胰岛素分泌之间的关系。
影响因子：
5.8
作者：
Ohta,M;Nelson,D;Nelson,J;Meglasson,MD;Erecińska,M
通讯作者：
Erecińska,M
DOI：
10.1016/s0021-9258(18)34936-6
发表时间：
1982-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
W E Jacobus;R W Moreadith;K M Vandegaer
通讯作者：
W E Jacobus;R W Moreadith;K M Vandegaer
透化 RINm5F 胰岛素瘤细胞中 ATP/ADP 比率和正磷酸盐对稳态游离 Ca2 水平的调节。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Corkey,BE;Deeney,JT;Glennon,MC;Matschinsky,FM;Prentki,M
通讯作者：
Prentki,M