Changes in intra-luminal calcium during spontaneous calcium waves following sensitization of ryanodine receptor channels.
Changes in intra-luminal calcium during spontaneous calcium waves following sensitization of ryanodine receptor channels.
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DOI：
10.4161/chan.4.2.11019
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Zima AV
中科院分区：
文献类型：
--
作者：
Domeier TL;Blatter LA;Zima AV
收缩期的心脏收缩依赖于动作电位触发的 Ca2+ 通过兰尼碱受体 (RyR) 通道从肌浆网 (SR) 释放。 SR Ca2+ 释放也可以在舒张期自发发生，这会导致 SR 内 Ca2+ 含量减少并导致心律失常发生。在这里，我们使用胞质 Ca2+ 和内部 SR Ca2+ ([Ca2+]SR) 的测量来检查 RyR 敏化如何改变兔心室肌细胞中自发的 SR Ca2+ 释放事件。咖啡因 (250 μM) 的 RyR 敏化增加了单个 RyR 通道的开放概率，增加了局部 SR Ca2+ 释放事件（Ca2+ 火花）的初始频率和幅度，并降低了 Ca2+ 火花终止处的 [Ca2+]SR 水平。在完整的肌细胞中，稳态电刺激后休息期间使用咖啡因会增加自发 Ca2+ 波的频率，并降低波终止处的 [Ca2+]SR 水平。这些影响导致 SR Ca2+ 含量显着下降。因此，增加 RyR 活性对心脏功能具有复杂的影响。收缩期 RyR 活性增加是有益的，因为它可以增加 SR Ca2+ 释放和收缩强度。然而，舒张期 RyR 活性增加会产生自发的、致心律失常的 Ca2+ 释放事件，从而降低 SR Ca2+ 含量，从而降低收缩力。
Cardiac contraction during systole is dependenton action potential-triggered Ca2+ release from the sarcoplasmic reticulum (SR) through ryanodine receptor (RyR) channels. SR Ca2+ release can also occur spontaneously during diastole, which causes a decrease in Ca2+ content within the SR and contributes to arrhythmogenesis. Here, we use measurements of cytosolic Ca2+ and intra-SR Ca2+ ([Ca2+]SR) to examine how RyR sensitization alters spontaneous SR Ca2+ release events in rabbit ventricular myocytes. RyR sensitization with caffeine (250 μM) increased the open probability of single RyR channels, increased the initial frequency and amplitude of local SR Ca2+ release events (Ca2+ sparks), and decreased the [Ca2+]SR level where Ca2+ sparks terminated. In intact myocytes, caffeine applied during rest after steady-state electrical stimulation increased the frequency of spontaneous Ca2+ waves and decreased the [Ca2+]SR level where waves terminated. These effects caused a marked loss of SR Ca2+ content. Therefore, increasing RyR activity has complex effects on cardiac function. Increased RyR activity during systole is beneficial as it increases SR Ca2+ release and contractile strength. However, increased RyR activity during diastole produces spontaneous, arrhythmogenic Ca2+ release events that lower SR Ca2+ content and subsequently decrease contractility.
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影响因子：
64.5
作者：
Marx, SO;Reiken, S;Marks, AR
通讯作者：
Marks, AR
影响因子：
3.4
作者：
MacQuaide, N.;Dempster, J.;Smith, G. L.
通讯作者：
Smith, G. L.
影响因子：
20.1
作者：
Zima AV;Picht E;Bers DM;Blatter LA
通讯作者：
Blatter LA
影响因子：
5.5
作者：
KASS, RS;LEDERER, WJ;WEINGART, R
通讯作者：
WEINGART, R
影响因子：
56.9
作者：
CHENG, H;LEDERER, WJ;CANNELL, MB
通讯作者：
CANNELL, MB