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静息后恢复过程中心肌激活时的钙内流和肌浆网钙释放

Ca influx and sarcoplasmic reticulum Ca release in cardiac muscle activation during postrest recovery.

作者信息

Bers D M

出版信息

Am J Physiol. 1985 Mar;248(3 Pt 2):H366-81. doi: 10.1152/ajpheart.1985.248.3.H366.

DOI:10.1152/ajpheart.1985.248.3.H366
PMID:2579587
Abstract

The recovery of twitch tension (T) and Ca influx after 5-s to 10-min rest intervals was studied in rabbit, rat, and frog cardiac muscle. Extracellular double-barreled Ca-selective microelectrodes were used to assess transsarcolemmal Ca influx. In rabbit ventricle, T at the first postrest beat (B1) exceeded T at the second beat (B2). T and Ca influx then increase toward steady state in a parallel fashion. Since Ca influx is small at B1, this beat may be more dependent on Ca stored in the sarcoplasmic reticulum (SR), and subsequent beats may more closely reflect Ca influx. We have examined this hypothesis using agents that may preferentially inhibit either SR Ca release or Ca influx. SR inhibitors caffeine (5 mM) and ryanodine (100 nM) changed the pattern of T recovery so that B1 was now less than B2 and more closely paralleled the recovery of Ca influx. Caffeine and ryanodine decreased steady-state T to 89 +/- 9 and 78 +/- 3%, respectively. In contrast, B1 was found to be less susceptible to inhibition than B2 when exposed to La or Co (influx inhibitors). These results are consistent with a rabbit ventricle model in which the SR Ca release contributes greatly to B1, the SR contribution declines while the Ca influx component increases, and Ca influx at steady state can account for a large fraction of steady-state T. In adult rat ventricle, caffeine and ryanodine decrease steady-state T to 33 +/- 2 and 13 +/- 3%, respectively, changing the T recovery pattern from a monotonic decrease to a monotonic increase. These results are consistent with a model qualitatively the same as rabbit ventricle. However, the SR can account for most of steady-state T in the rat, and thus its decaying characteristic dominates the control postrest recovery. By inhibition of SR Ca release, the increasing component ascribed to Ca influx becomes apparent. Similar experiments were done to establish an order of relative dependence on SR Ca release: adult rat ventricle greater than rabbit atrium greater than rabbit ventricle greater than frog ventricle.

摘要

我们研究了兔、大鼠和蛙心肌在5秒至10分钟的休息间隔后抽搐张力(T)和钙内流的恢复情况。使用细胞外双管钙选择性微电极评估跨肌膜钙内流。在兔心室中,休息后第一个搏动(B1)时的T超过第二个搏动(B2)时的T。然后T和钙内流以平行方式朝着稳态增加。由于B1时钙内流较少,该搏动可能更依赖于肌浆网(SR)中储存的钙,而随后的搏动可能更紧密地反映钙内流。我们使用可能优先抑制SR钙释放或钙内流的药物检验了这一假设。SR抑制剂咖啡因(5 mM)和兰尼碱(100 nM)改变了T恢复模式,使得现在B1小于B2,并且更紧密地与钙内流的恢复平行。咖啡因和兰尼碱分别将稳态T降低至89±9%和78±3%。相比之下,当暴露于镧或钴(内流抑制剂)时,发现B1比B2更不易受到抑制。这些结果与兔心室模型一致,在该模型中,SR钙释放对B1有很大贡献,SR的贡献下降而钙内流成分增加,并且稳态时的钙内流可占稳态T的很大一部分。在成年大鼠心室中,咖啡因和兰尼碱分别将稳态T降低至33±2%和13±3%,将T恢复模式从单调下降变为单调增加。这些结果与一个在性质上与兔心室相同的模型一致。然而,SR可占大鼠稳态T的大部分,因此其衰减特性主导了休息后恢复的控制。通过抑制SR钙释放,归因于钙内流的增加成分变得明显。进行了类似的实验以确定对SR钙释放的相对依赖顺序:成年大鼠心室大于兔心房大于兔心室大于蛙心室。

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