Dual effects of tetracaine on spontaneous calcium release in rat ventricular myocytes.
Dual effects of tetracaine on spontaneous calcium release in rat ventricular myocytes.
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丁卡因对大鼠心室肌细胞自发钙释放的双重作用。
DOI：
10.1113/jphysiol.1997.sp022021
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Györke,I
中科院分区：
文献类型：
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作者：
Györke,S;Lukyanenko,V;Györke,I
1.用共聚焦显微荧光法研究了丁卡因对离体大鼠心室肌细胞肌浆网（SR）自发性钙释放的影响。2.在低浓度（0.25 - 1.25 mM）下，丁卡因会引起自发释放事件（Ca 2+火花）和Ca 2+波的初始抑制，随后Ca 2+释放活性逐渐增加。火花的频率和幅度首先降低，然后相对于控制水平增加。在高浓度（> 1.25 mM）下，丁卡因消除了所有形式的自发释放。3.心肌细胞暴露于丁卡因导致SR Ca 2+负荷逐渐增加，如咖啡因诱导的Ca 2+瞬变幅度变化所示。4.在心脏SR Ca（2+）释放通道中，丁卡因（> 0.25 mM）可诱导稳定的通道活性抑制。在控制条件下以及在各种浓度的丁卡因存在下，向通道的腔侧添加毫摩尔Ca 2+引起通道开放概率增加。5.我们得出结论，丁卡因对SR Ca（2+）释放通道的主要作用是抑制体外和原位通道活性。丁卡因降低火花幅度的能力表明，这些事件不是由于单个通道或不可还原的通道簇的激活，因此支持火花的多通道起源。我们提出，次最大浓度丁卡因释放的矛盾晚期增强是由SR Ca 2+负荷的逐渐增加和随后SR内Ca 2+激活Ca（2+）释放通道引起的。
1. Confocal microfluorometry was used to study the effects of tetracaine on spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) in isolated rat ventricular myocytes. 2. At low concentrations (0.25‐1.25 mM), tetracaine caused an initial inhibition of spontaneous release events (Ca2+ sparks) and Ca2+ waves, which was followed by a gradual increase in Ca2+ release activity. The frequency and magnitude of sparks were first decreased and then increased with respect to control levels. At high concentrations (> 1.25 mM), tetracaine abolished all forms of spontaneous release. 3. Exposure of the myocytes to tetracaine resulted in a gradual increase in the SR Ca2+ load as indexed by changes in the magnitude of caffeine‐induced Ca2+ transients. 4. In cardiac SR Ca(2+)‐release channels incorporated into lipid bilayers, tetracaine (> 0.25 mM) induced a steady inhibition of channel activity. Addition of millimolar Ca2+ to the luminal side of the channel caused an increase in channel open probability under control conditions as well as in the presence of various concentrations of tetracaine. 5. We conclude that the primary effect of tetracaine on SR Ca(2+)‐release channels is inhibition of channel activity both in vitro and in situ. The ability of tetracaine to reduce spark magnitude suggests that these events are not due to activation of single channels or non‐reducible clusters of channels and, therefore, supports the multichannel origin of sparks. We propose that the paradoxical late potentiation of release by submaximal concentrations of tetracaine is caused by a gradual increase in SR Ca2+ load and subsequent activation of the Ca(2+)‐release channels by Ca2+ inside the SR.