Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels.
Antidiabetic sulfonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP-dependent K+ channels.
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DOI：
10.1016/s0021-9258(18)68422-4
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发表时间：
1988-06
期刊：
影响因子：
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通讯作者：
M. Fosset;J. R. Weille;R. D. Green;H. Schmid-Antomarchi;M. Lazdunski
中科院分区：
文献类型：
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作者：
M. Fosset;J. R. Weille;R. D. Green;H. Schmid-Antomarchi;M. Lazdunski
鸟类和哺乳动物心脏细胞都具有抗糖尿病磺脲类药物的高亲和力受体。用[3H]格列本脲对这些受体进行了生化鉴定。最有效的磺脲类药物，如格列本脲本身的Kd值在纳摩尔范围内。结构-功能关系的比较研究表明，磺酰脲受体在心脏细胞和胰岛素瘤细胞中的结合特性高度相似。豚鼠心肌细胞的动作电位持续时间通过灌注或氧化磷酸化阻断而显著降低细胞内ATP浓度。格列本脲可使[ATP]衰竭的心肌细胞恢复正常或接近正常的动作电位特性。使用膜片钳技术的单通道记录表明，这种效应与磺脲类药物对atp敏感的K+通道的高亲和力阻断有关。
Both avian and mammalian heart cells have high affinity receptors for antidiabetic sulfonylureas. The biochemical identification of these receptors has been carried out with [3H]glibenclamide. The Kd values for the most potent sulfonylureas, such as glibenclamide itself, are in the nanomolar range. Comparative studies of structure-function relationships indicate high similarities of binding properties between the sulfonylurea receptors in cardiac cells and insulinoma cells, respectively. The duration of the action potential of guinea pig cardiac cells was drastically reduced by decreasing intracellular ATP concentrations by perfusion or by blockade of oxidative phosphorylation. Glibenclamide was found to restore normal or nearly normal action potential properties in [ATP]in-depleted cardiac cells. Single channel recording using the patch-clamp technique has shown that this effect is associated with high affinity blockade of ATP-sensitive K+ channels by sulfonylureas.