Voltage-independent changes in L-type Ca(2+) current uncoupled from SR Ca(2+) release in cardiac myocytes.
Voltage-independent changes in L-type Ca(2+) current uncoupled from SR Ca(2+) release in cardiac myocytes.
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L 型 Ca(2 ) 电流的电压依赖性变化与心肌细胞中 SR Ca(2 ) 释放无关。
DOI：
10.1152/ajpheart.2000.279.4.h2024
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Stern,MD
中科院分区：
文献类型：
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作者：
Janczewski,AM;Lakatta,EG;Stern,MD
为了确定L型钙电流（伊卡）的电压依赖性改变对心肌细胞肌浆网（SR）钙释放的影响，我们测量了ICa和胞浆钙瞬变（Cai 2 +;在1）细胞外[Ca 2 +]（Cao 2+）突然增加或2）应用1 μM FPL-64176期间，一种钙通道激动剂，选择性地改变SR钙负荷的变化。在高Ca ~（2+）时，第一次除极时峰值Ca ~（2+）增加46 ± 6%（P< 0.001），但Ca ~（2+）最大上升速率（dCa ~（2+）/dtmax）和Ca ~（2+）瞬时振幅的增加不显著。快速暴露于FPL-64176大大减缓了ICa的失活，使其时间积分增加了117 ± 8%（P< 0.001），而没有显著增加峰值ICa、dCai 2 +/dtmax或相应Cai 2+瞬变的幅度。延长高Ca ~（2+）或FPL-64176的暴露时间，不能进一步增加峰电流，但可显著增加钙离子释放的dCa ~（2+）/dtmax、Ca ~（2+）瞬时振幅和钙离子释放增益（dCa ~（2+）/dtmax/伊卡），这显然是由于SR Ca ~（2+）负荷增加所致。持续高浓度Ca 2+（37 ± 5%，P < 0.001）或FPL-64176（63 ± 5%，P < 0.002）使dCa 2 +/dtmax达峰时间显著延长。我们的实验提供了第一个证据，一个显着的差距之间的增加peakICa和相应的SR Ca 2+释放。我们把这归因于饱和的SR Ca 2+释放通量预测的局部控制理论。更大的ICa和最大程度增加的SR Ca 2+负荷的联合作用导致SR Ca 2+释放通量的延长，可能反映了来自Corbular SR的额外Ca 2+释放。
To determine the effect of voltage-independent alterations of L-type Ca2+current (ICa) on the sarcoplasmic reticular (SR) Ca2+release in cardiac myocytes, we measuredICaand cytosolic Ca2+transients (Cai2+; intracellular Ca2+concentration) in voltage-clamped rat ventricular myocytes during1) an abrupt increase of extracellular [Ca2+] (Cao2+) or2) application of 1 μM FPL-64176, a Ca2+channel agonist, to selectively alterICain the absence of changes in SR Ca2+loading. On the first depolarization in higher Cao2+, peakICawas increased by 46 ± 6% (P< 0.001), but the increases in the maximal rate of rise of Cai2+(dCai2+/dtmax, wheretis time; an index of SR Ca2+release flux) and the Cai2+transient amplitude were not significant. Rapid exposure to FPL-64176 greatly slowed inactivation ofICa, increasing its time integral by 117 ± 8% (P< 0.001) without significantly increasing peakICa, dCai2+/dtmax, or amplitude of the corresponding Cai2+transient. Prolongation of exposure to higher Cao2+or FPL-64176 did not further increase peakICabut greatly increased dCai2+/dtmax, Cai2+transient amplitude, and the gain of Ca2+release (dCai2+/dtmax/ICa), evidently due to augmentation of the SR Ca2+loading. Also, the time to peak dCai2+/dtmaxwas significantly increased in the continuous presence of higher Cao2+(by 37 ± 5%,P< 0.001) or FPL-64176 (by 63 ± 5%,P< 0.002). Our experiments provide the first evidence of a marked disparity between an increased peakICaand the corresponding SR Ca2+release. We attribute this to saturation of the SR Ca2+release flux as predicted by local control theory. Prolongation of the SR Ca2+release flux, caused by combined actions of a largerICaand maximally augmented SR Ca2+loading, might reflect additional Ca2+release from corbular SR.