Voltage dependence of Ca2+ sparks in intact cerebral arteries
Voltage dependence of Ca2+ sparks in intact cerebral arteries
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DOI：
10.1152/ajpcell.1998.274.6.c1755
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发表时间：
1998-06-01
影响因子：
5.5
通讯作者：
Nelson, MT
中科院分区：
文献类型：
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作者：
Jaggar, JH;Stevenson, AS;Nelson, MT
Ca2+火花先前已在分离的平滑肌细胞中被描述。在此，我们首次对完整平滑肌标本中的局部Ca2+瞬变（“Ca2+火花”）进行了测量。Ca2+火花似乎是由肌浆网（SR）中对兰尼碱敏感的Ca2+释放（RyR）通道开放所导致。使用荧光Ca2+指示剂fluo 3和激光扫描共聚焦显微镜测量了大鼠完整脑动脉（直径40 - 150μm）中的细胞内Ca2+浓度（[Ca2+](i)）。通过将细胞外K+从6 mM升高到30 mM使膜电位去极化，增加了Ca2+火花的频率（4.3倍）和幅度（约2倍）以及整个动脉壁的[Ca2+](i)（约1.7倍）。衰减半衰期（约50 ms）不受膜电位去极化的影响。兰尼碱（10μM）可抑制分离细胞中的RyR通道和Ca2+火花，毒胡萝卜素（100 nM）通过阻断肌浆网Ca2+-ATP酶间接抑制RyR通道，它们完全抑制了完整脑动脉中的Ca2+火花。地尔硫卓是一种电压依赖性Ca2+通道抑制剂，它以浓度依赖的方式降低了完整脑动脉中的整体[Ca2+](i)以及Ca2+火花的频率和幅度。Ca2+火花的频率（
Ca2+ sparks have been previously described in isolated smooth muscle cells. Here we present the first measurements of local Ca2+ transients ("Ca2+ sparks") in an intact smooth muscle preparation. Ca2+ sparks appear to result from the opening of ryanodine-sensitive Ca2+ release (RyR) channels in the sarcoplasmic reticulum (SR). Intracellular Ca2+ concentration ([Ca2+](i)) was measured in intact cerebral arteries (40-150 mu m in diameter) from rats, using the fluorescent Ca2+ indicator fluo 3 and a laser scanning confocal microscope. Membrane potential depolarization by elevation of external K+ from 6 to 30 mM increased Ca2+ spark frequency (4.3-fold) and amplitude (similar to 2-fold) as well as global arterial wall [Ca2+](i) (similar to 1.7-fold). The half time of decay (similar to 50 ms) was not affected by membrane potential depolarization. Ryanodine (10 mu M), which inhibits RyR channels and Ca2+ sparks in isolated cells, and thapsigargin (100 nM), which indirectly inhibits RyR channels by blocking the SR Ca2+-ATPase, completely inhibited Ca2+ sparks in intact cerebral arteries. Diltiazem, an inhibitor of voltage-depen dent Ca2+ channels, lowered global [Ca2+](i) and Ca2+ spark frequency and amplitude in intact cerebral arteries in a concentration-dependent manner. The frequency of Ca2+ sparks (