Depressed ryanodine receptor activity increases variability and duration of the systolic Ca2+ transient in rat ventricular myocytes
Depressed ryanodine receptor activity increases variability and duration of the systolic Ca2+ transient in rat ventricular myocytes
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DOI：
10.1161/01.res.0000035527.53514.c2
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发表时间：
2002-10-04
影响因子：
20.1
通讯作者：
O'Neill, SC
中科院分区：
文献类型：
--
作者：
Díaz, ME;Eisner, DA;O'Neill, SC
肌浆网（SR）通过Ryanodine受体（RyR）释放的Ca 2+对于收缩期Ca 2+瞬变和心脏收缩功能是必需的。本研究的目的是检查抑制RyR开放概率（P.）对收缩期Ca 2+瞬变空间组织的影响。丁卡因或细胞内酸化。使用共聚焦显微镜研究了电压钳位，Fluo-3负载的肌细胞。抑制RyR P-o增加了细胞不同区域之间Ca 2+瞬时振幅的变异性。这种变化经常产生交替，一个区域交替产生大的和小的瞬变。此外，Ca 2+瞬变的升高阶段变为双相。初始相位是恒定的，但第二个是可变的，并作为波通过部分细胞传播。这两个阶段都涉及SR Ca 2+释放，这一点通过咖啡因减少它们来证明。区域[Ca 2 +]（i）交替伴随着一个小得多的程度交替在整个细胞水平。我们认为，在丁卡因或酸中毒，Ca 2+瞬变的初始阶段的结果从Ca 2+释放通过RyRs直接激活相邻的L-型Ca 2+通道。在某些位点，这将激活邻近的RyR，并且Ca 2+波将通过激活其他RyR传播。这项工作是第一次证明，减少RyR P。单独可以产生混乱的Ca 2+释放过程，并启动交替。
Sarcoplasmic reticulum (SR) Ca2+ release, through the ryanodine receptor (RyR), is essential for the systolic Ca2+ transient and thus the cardiac contractile function. The aim of this study was to examine the effects on the spatial organization of the systolic Ca2+ transient of depressing RyR open probability (P.) with tetracaine or intracellular acidification. Voltage-clamped, fluo-3-loaded myocytes were studied using confocal microscopy. Depressing RyR P-o increased the variability of the Ca2+ transient amplitude between different regions of the cell. This variability often produced alternans with a region producing large and small transients alternately. In addition, the raising phase of the Ca2+ transient became biphasic. The initial phase was constant but the second was variable and propagated as a wave through part of the cell. That both phases involved SR Ca2+ release was shown by their reduction by caffeine. Regional [Ca2+](i) alternans was accompanied by a much smaller degree of alternans at the whole cell level. We suggest that, in tetracaine or acidosis, the initial phase of the Ca2+ transient results from Ca2+ release via RyRs directly activated by adjacent L-type Ca2+ channels. At some sites, this will activate neighboring RyRs and a Ca2+ wave will propagate via activation of other RyRs. This work is the first demonstration that decreased RyR P. alone can produce disarray of the Ca2+ release process and initiate alternans.