Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps.
Palytoxin disrupts cardiac excitation-contraction coupling through interactions with P-type ion pumps.
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海藻毒素通过与 P 型离子泵的相互作用破坏心脏兴奋-收缩耦合。
DOI：
10.1152/ajpcell.00541.2003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Blatter,LotharA
中科院分区：
文献类型：
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作者：
Kockskämper,Jens;Ahmmed,GiasU;Zima,AlekseyV;Sheehan,KatherineA;Glitsch,HelfriedG;Blatter,LotharA
海葵毒素是一种严重损害心脏功能的珊瑚毒素，但其对兴奋-收缩（E-C）偶联的影响仍然难以捉摸。因此，我们研究了海葵毒素对心房电-心耦合机制的影响。在电场刺激的猫心房肌细胞中，海葵毒素引起舒张期细胞内Ca ~（2+）浓度（[Ca ~（2+）]i）升高，[Ca ~（2+）] i瞬时振幅降低，Ca ~（2+）交替出现[Ca ~（2+）] i波，Ca ~（2+）释放失败。尽管肌浆网（SR）钙负荷高，[Ca 2 +] i瞬态幅度仍发生下降。在电压钳位心肌细胞中，海葵毒素诱导的电流具有线性电流-电压关系（反转电位<5 mV），该电流被哇巴因阻断。全细胞Ca ~（2+）电流和ryanodine受体Ca ~（2+）释放通道功能不受毒素的影响。然而，palytoxin显着降低钙泵孤立SR囊泡。在电流钳刺激在1 Hz的心肌细胞，海葵毒素诱导的静息膜电位，伴随着延迟后去极化的去极化。未观察到动作电位构型的重大变化。结果表明，海葵毒素干扰肌膜Na ~+-K ~+泵和SR Ca ~（2+）泵的功能。所建议的心房中的沙冬青毒素毒性模式涉及Na+-K+泵转化为非选择性阳离子通道作为主要事件，随后是去极化、Na+蓄积和Ca 2+过载，这反过来又引起致心律失常[Ca 2 +] i波和延迟的后去极化。
Palytoxin is a coral toxin that seriously impairs heart function, but its effects on excitation-contraction (E-C) coupling have remained elusive. Therefore, we studied the effects of palytoxin on mechanisms involved in atrial E-C coupling. In field-stimulated cat atrial myocytes, palytoxin caused elevation of diastolic intracellular Ca2+concentration ([Ca2+]i), a decrease in [Ca2+]itransient amplitude, Ca2+alternans followed by [Ca2+]iwaves, and failures of Ca2+release. The decrease in [Ca2+]itransient amplitude occurred despite high sarcoplasmic reticulum (SR) Ca2+load. In voltage-clamped myocytes, palytoxin induced a current with a linear current-voltage relationship (reversal potential ∼5 mV) that was blocked by ouabain. Whole cell Ca2+current and ryanodine receptor Ca2+release channel function remained unaffected by the toxin. However, palytoxin significantly reduced Ca2+pumping of isolated SR vesicles. In current-clamped myocytes stimulated at 1 Hz, palytoxin induced a depolarization of the resting membrane potential that was accompanied by delayed afterdepolarizations. No major changes of action potential configuration were observed. The results demonstrate that palytoxin interferes with the function of the sarcolemmal Na+-K+pump and the SR Ca2+pump. The suggested mode of palytoxin toxicity in the atrium involves the conversion of Na+-K+pumps into nonselective cation channels as a primary event followed by depolarization, Na+accumulation, and Ca2+overload, which, in turn, causes arrhythmogenic [Ca2+]iwaves and delayed afterdepolarizations.