Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis.
Cardiac ATP-sensitive K+ channels. Evidence for preferential regulation by glycolysis.
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DOI：
10.1085/jgp.94.5.911
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发表时间：
1989-11
影响因子：
3.8
通讯作者：
LAMP, ST
中科院分区：
文献类型：
--
作者：
WEISS, JN;LAMP, ST
在膜片钳单个豚鼠心室肌细胞中比较了糖酵解、氧化磷酸化、肌酸激酶系统和外源性ATP抑制ATP敏感性K+通道和防止细胞缩短的能力。在一端用皂苷透化的肌细胞上的细胞贴附贴片中，ATP敏感性K+通道通过从浴中去除ATP而被激活，并且可以被外源性ATP或通过糖酵解（存在线粒体抑制剂FCCP）、线粒体氧化磷酸化或肌酸激酶系统产生内源性ATP的底物同样良好地关闭。然而，在存在外源性ATP消耗系统的情况下，糖酵解底物（存在FCCP）在抑制ATP敏感性K+通道方面上级于氧化磷酸化或肌酸激酶系统的底物。所有三组底物在防止细胞缩短方面同样有效。在38个切除的由内而外的膜补丁，ATP敏感的K+通道激活，从浴中去除ATP抑制了一套完整的底物的ATP生产步骤的糖酵解，但不是由个人的糖酵解底物，这是一致的关键糖酵解酶的存在下，位于附近的通道，在这些补丁。在全细胞电压钳条件下，在透析细胞内部的贴片电极溶液中加入15 mM ATP并不能阻止在对照条件下或暴露于完全代谢抑制期间ATP敏感性K+电流的激活。在离体动脉灌注兔室间隔，糖酵解的选择性抑制引起42 K+流出率的立即增加，这是防止由100 μ M格列本脲，一个已知的ATP敏感性K+通道阻滞剂。这些观察结果表明，关键的糖酵解酶与心脏。ATP敏感性K+通道和在细胞内竞争ATP高的条件下（例如，在跳动心脏中），其充当这些通道的ATP的优先来源。
The ability of glycolysis, oxidative phosphorylation, the creatine kinase system, and exogenous ATP to suppress ATP-sensitive K+ channels and prevent cell shortening were compared in patch-clamped single guinea pig ventricular myocytes. In cell-attached patches on myocytes permeabilized at one end with saponin, ATP-sensitive K+ channels were activated by removing ATP from the bath, and could be closed equally well by exogenous ATP or substrates for endogenous ATP production by glycolysis (with the mitochondrial inhibitor FCCP present), mitochondrial oxidative phosphorylation, or the creatine kinase system. In the presence of an exogenous ATP-consuming system, however, glycolytic substrates (with FCCP present) were superior to substrates for either oxidative phosphorylation or the creatine kinase system at suppressing ATP-sensitive K+ channels. All three groups of substrates were equally effective at preventing cell shortening. In 6 of 38 excised inside-out membrane patches, ATP-sensitive K+ channels activated by removing ATP from the bath were suppressed by a complete set of substrates for the ATP-producing steps of glycolysis but not by individual glycolytic substrates, which is consistent with the presence of key glycolytic enzymes located near the channels in these patches. Under whole-cell voltage-clamp conditions, inclusion of 15 mM ATP in the patch electrode solution dialyzing the interior of the cell did not prevent activation of the ATP-sensitive K+ current under control conditions or during exposure to complete metabolic inhibition. In isolated arterially perfused rabbit interventricular septa, selective inhibition of glycolysis caused an immediate increase in 42K+ efflux rate, which was prevented by 100 microM glyburide, a known blocker of ATP-sensitive K+ channels. These observations suggest that key glycolytic enzymes are associated with cardiac. ATP-sensitive K+ channels and under conditions in which intracellular competition for ATP is high (e.g., in beating heart) that act as a preferential source of ATP for these channels.
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影响因子：
20.1
作者：
BRICKNELL, OL;OPIE, LH
通讯作者：
OPIE, LH
DOI：
10.1016/s0022-2828(84)80014-0
发表时间：
1984-01-01
影响因子：
5
作者：
HASIN, Y;DOOREY, A;BARRY, WH
通讯作者：
BARRY, WH
影响因子：
2.8
作者：
HEARSE, DJ
通讯作者：
HEARSE, DJ
影响因子：
3.5
作者：
KAKEI, M;KELLY, RP;ASHCROFT, FM
通讯作者：
ASHCROFT, FM
影响因子：
56.9
作者：
LYNCH, RM;PAUL, RJ
通讯作者：
PAUL, RJ