A metabolic control mechanism for calcium ion influx that may protect the ventricular myocardial cell.
A metabolic control mechanism for calcium ion influx that may protect the ventricular myocardial cell.
复制标题
钙离子流入的代谢控制机制可以保护心室心肌细胞。
DOI：
10.1016/0002-9149(76)90428-8
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发表时间：
1976
期刊：
影响因子：
--
通讯作者：
Joel A. Schneider
中科院分区：
文献类型：
--
作者：
Nick Sperelakis;Joel A. Schneider
在动作电位过程中，钙离子流入心肌细胞，启动并控制收缩程度。Ca~(++)内流导致肌浆内游离Ca~(++)浓度增加到约10−~5摩尔，从而激活肌原纤维；Ca~(++)也可通过Ca~(++)内流或跨膜电压变化从肌浆网中释放出来。动作电位平台期间的内向钙电流穿过一组单独的慢阳离子通道，与快钠离子通道相比，这些通道具有一些特殊的特性：慢通道对河豚毒素不敏感，激活和失活电位较低，动力学上较慢(缓慢的激活、失活和恢复过程)。慢钙通道需要代谢能量，并被维拉帕米、锰离子、镧离子和酸中毒所阻断。当快速Na+通道被河豚毒素阻断或电压被27毫摩尔钾离子灭活时，兴奋性丧失，但可被儿茶酚胺和甲基黄嘌呤恢复：传播缓慢上升的电反应(伴随收缩)，类似于正常动作电位的平台。正性肌力药如去甲肾上腺素、茶碱和组胺似乎通过升高环腺苷一磷酸(AMP)水平和增加可用于电压激活的Ca++通道数量而起作用。增加的cAMP可通过cAMP依赖的蛋白激酶和三磷酸腺苷(ATP)导致慢通道的膜蛋白成分的磷酸化。因此，心肌细胞对可用慢通道的数量进行控制，从而控制每个脉冲的钙离子内流。这种调控机制可以通过减少钙离子的内流和收缩来保护心肌细胞的三磷酸腺苷，从而防止受影响的细胞工作到死亡。缺血细胞内的钙通道可因ATP降低、pH降低或其他代谢物积聚而不起作用。
Calcium ion influx into the myocardial cell during the action potential initiates and controls the degree of contraction. The Ca++influx leads to an increase of the myoplasmic free Ca++concentration to about 10−5molar for activation of the myofibrils; Ca++may also be released from the sarcoplasmic reticulum by the entering Ca++or by voltage change across its membrane. The inward Ca++current during the action potential plateau traverses the sarcolemma through a separate set of slow cation channels that have some peculiar properties compared to fast sodium ion channels: Slow channels are not sensitive to tetrodotoxin, have lower activation and inactivation potentials and are kinetically slow (slow activation, inactivation and recovery processes). Slow Ca++channels require metabolic energy and are blocked by verapamil, manganese ion, lanthanum ion and acidosis. When the fast Na++channels are blocked by tetrodotoxin or voltage inactivated by 27 millimolar potassium ion, excitability is lost but can be restored by catecholamines and methylxanthines: Propagating slowly rising electrical responses (accompanied by contractions) occur that resemble the plateau of the normal action potential.Positive inotropic agents such as norepinephrine, theophylline and histamine appear to act by elevating cyclic adenosine monophosphate (AMP) levels and increasing the number of Ca++channels available for voltage activation. Increased cyclic AMP could lead to phosphorylation of a membrane protein constituent of the slow channels by means of a cyclic AMP-dependent protein kinase and adenosine triphosphate (ATP). Thus, the myocardial cell exercises control over the number of available slow channels and, hence, the Ca++influx per impulse. This control mechanism could serve to protect the myocardial cell during periods of regional ischemia by acting to conserve ATP through reduced Ca++influx and contraction, and thus preventing the affected cells from working themselves to death. The Ca++channels in ischemic cells could be made inoperative by decreased ATP, decreased pH or accumulation of some other metabolite.