RELAXATION IN RABBIT AND RAT CARDIAC-CELLS - SPECIES-DEPENDENT DIFFERENCES IN CELLULAR MECHANISMS
RELAXATION IN RABBIT AND RAT CARDIAC-CELLS - SPECIES-DEPENDENT DIFFERENCES IN CELLULAR MECHANISMS
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DOI：
10.1113/jphysiol.1994.sp020130
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发表时间：
1994-04-15
影响因子：
5.5
通讯作者：
BERS, DM
中科院分区：
文献类型：
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作者：
BASSANI, JWM;BASSANI, RA;BERS, DM
比较了分离兔和大鼠心室肌细胞在咖啡因收缩和电刺激抽搐时，肌浆网Ca2+- atp酶和Na+-Ca2+交换在细胞质中Ca2+去除的作用。细胞缩短和细胞内钙浓度（[Ca2+](i)）的测量在印度-1负载的细胞。外部Na+被Li+取代，Na+-Ca2+交换被抑制。为了避免在0Na +溶液中抽搐期间细胞或SR Ca2+负荷的净变化，使用0Na(+), 0 ca（2+）溶液长时间预灌注耗尽细胞内Na+ (Na-1(+))。咖啡因或TG均能抑制SR Ca2+的积累。在Na-1（+）耗竭前后，大鼠的稳态抽搐放松速度比家兔快2倍。相比之下，咖啡因收缩（SR Ca2+积累被抑制），在兔细胞中放松得更快。在兔和大鼠肌细胞中，去除外部Naf分别使咖啡因挛缩松弛的半时间增加了15倍和5倍（仅在兔细胞中增加了挛缩幅度）。两种植物在0 Na+、0 Ca2+溶液中的弛豫时间过程相似。在抽搐期间抑制Na+-Ca-2交换使兔肌细胞的[Ca2+](i)瞬态振幅（δ [Ca2+](i)）增加50%，[Ca2+](i)下降的时间常数（tau）增加45%。在0 Na+溶液中，观察到大鼠细胞中tau蛋白（20%）的增加较小，δ [Ca2+](i)没有变化。[Ca2+](i)在大鼠细胞中的瞬变速度更快。在抽搐期间SR Ca2+- atp酶的抑制使两种物种的δ [Ca2+](i)增加25%。大鼠暴露于TG后tau蛋白的增加（9倍）大于兔肌细胞（2倍），这导致大鼠的[Ca2+](i)下降速度比兔细胞慢70%。tg处理的细胞在抽搐期间[Ca2+](i)下降的时间过程与咖啡因处理的对照细胞相似。这些Ca2+运输系统的联合抑制显着减缓了[Ca2+](i)下降的时间过程，因此tau在两个物种中几乎相同，与在0 Na+， 0 Ca2+溶液中应用咖啡因时相当。因此，在这些物种中，缓慢的Ca2+运输机制（线粒体Ca2+摄取和肌上皮Ca2+- atp酶）的共同参与是相似的。我们得出结论，在[Ca2+](i)短暂下降过程中，兔的Na+-Ca2+交换速度比大鼠快2- s倍，而大鼠的XR Ca2+- atp酶速度快2- 3倍。虽然SR Ca2+- atp酶在两种细胞类型中都比Na+-Ca2+交换更强大，但在大鼠中的优势更为明显（类似于13倍对2.5倍）。最后，我们估计在抽搐过程中，SR、Na+-Ca2+交换和慢速系统运输的Ca2+的比例在兔肌细胞中分别为70、28和2%，在大鼠肌细胞中分别为92、7和1%。
The roles of the sarcoplasmic reticulum (SR) Ca2+-ATPase and Na+-Ca2+ exchange in Ca2+ removal from cytosol were compared in isolated rabbit and rat ventricular myocytes during caffeine contractures and electrically stimulated twitches. Cell shortening and intracellular calcium concentration ([Ca2+](i)) were measured in indo-1-loaded cells.2. Na+-Ca2+ exchange was inhibited by replacement of external Na+ by Li+. To avoid net changes in cell or SR Ca2+ load during a twitch in 0 Na+ solution, intracellular Na+ (Na-1(+)) was depleted using a long pre-perfusion with 0Na(+), 0Ca(2+) solution. SR Ca2+ accumulation was inhibited by caffeine or thapsigargin (TG).3. Relaxation of steady-state twitches was 2-fold faster in rat than in rabbit (before and after Na-1(+) depletion). In contrast, caffeine contractures (where SR Ca2+ accumulation is inhibited), relaxed faster in rabbit cells. Removal of external Naf increased the half-time for relaxation of caffeine contractures 15- and 5-fold in rabbit and rat myocytes respectively (and increased contracture amplitude in rabbit cells only). The time course of relaxation in 0 Na+, 0 Ca2+ solution was similar in the two species.4. Inhibition of the Na+-Ca-2 exchange during a twitch increased the [Ca2+](i) transient amplitude (Delta[Ca2+](i)) by 50 % and the time constant of [Ca2+](i) decline (tau) by 45% in rabbit myocytes. A smaller increase in tau (20%) and no change in Delta[Ca2+](i) were observed in rat cells in 0 Na+ solution. [Ca2+](i) transients remained more rapid in rat cells.5. Inhibition of the SR Ca2+-ATPase during a twitch enhanced Delta[Ca2+](i) by 25% in both species. The increase in tau after TG exposure was greater in rat (9-fold) than in rabbit myocytes (2-fold), which caused [Ca2+](i) decline to be 70% slower in rat compared with rabbit cells. The time course of [Ca2+](i) decline during twitch in TG-treated cells was similar to that during caffeine application in control cells.6. Combined inhibition of these Ca2+ transport systems markedly slowed the time course of [Ca2+](i) decline, so that tau was virtually the same in both species and comparable to that during caffeine application in 0 Na+, 0 Ca2+ solution. Thus, the combined participation of slow Ca2+ transport mechanisms (mitochondrial Ca2+ uptake and sarcolemmal Ca2+- ATPase) is similar in these species.7. We conclude that during the decline of the [Ca2+](i) transient, the Na+-Ca2+ exchange is about 2- to S-fold faster in rabbit than in rat, whereas the XR Ca2+-ATPase is 2- to 3-fold faster in the rat. While the SR Ca2+-ATPase is more powerful than the Na+-Ca2+ exchange in both cell types the dominance is much more marked in rat(similar to 13-fold vs. 2.5-fold in rabbit). Finally we estimate that the fraction of Ca2+ transported by the SR, Na+-Ca2+ exchange and slow systems during a twitch are 70, 28 and 2% respectively in rabbit myocytes and 92, 7 and 1% respectively in rat myocytes.