The cellular force-frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus.
The cellular force-frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus.
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巨蜥蜥蜴（Varanus exanthematicus）心室肌细胞的细胞力-频率响应。
DOI：
10.1152/ajpregu.00650.2009
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Shiels,HollyA
中科院分区：
文献类型：
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作者：
Warren,DanielE;Galli,GinaLJ;Patrick,SimonM;Shiels,HollyA
为探讨变种蜥蜴脑室负力-频率关系(FFR)的细胞机制，我们测定了分离的心室肌细胞的肌节和细胞缩短、细胞内钙离子([Ca+]i)、动作电位(APs)和钾电流。实验在0.2到1.0赫兹之间进行，这一频率跨越了该物种在20-22°C的活体心率的生理范围。随着刺激频率的增加，舒张期长度、肌节长度变化率和松弛时间均显著减小。缩短速度未受影响。这些变化对应于[Ca~(2+)]i升高的速度加快，[Ca~(2+)]瞬时幅度降低，舒张期[Ca~(2+)]i增加7倍。钙瞬变的衰减时间常数(τ)在高频时减小，显示频率依赖性的松弛加速(FDAR)，但在中频时达到平台期，在0.5赫兹以上无变化。AP上升速率不受影响，AP时程(APd)随频率增加而缩短。除极峰值有降低的趋势，但仅在1.0赫兹时显著。动作电位时程的降低不是由于延迟内向整流(IKr)或瞬时外向电流(Ito)的频率依赖性改变，因为两者似乎都不存在于Varanid心室肌细胞中。我们的结果表明，变种蜥蜴心室肌的负FFR关系是由于钙瞬变的幅度降低，加上舒张期钙的增加，从而导致高频搏动之间的不完全松弛。这与更高频率的时程缩短不谋而合。
To investigate the cellular mechanisms underlying the negative force-frequency relationship (FFR) in the ventricle of the varanid lizard, Varanus exanthematicus, we measured sarcomere and cell shortening, intracellular Ca2+([Ca2+]i), action potentials (APs), and K+currents in isolated ventricular myocytes. Experiments were conducted between 0.2 and 1.0 Hz, which spans the physiological range of in vivo heart rates at 20–22°C for this species. As stimulation frequency increased, diastolic length, percent change in sarcomere length, and relaxation time all decreased significantly. Shortening velocity was unaffected. These changes corresponded to a faster rate of rise of [Ca2+]i, a decrease in [Ca2+]itransient amplitude, and a seven-fold increase in diastolic [Ca2+]i. The time constant for the decay of the Ca2+transient (τ) decreased at higher frequencies, indicating a frequency-dependent acceleration of relaxation (FDAR) but then reached a plateau at moderate frequencies and did not change above 0.5 Hz. The rate of rise of the AP was unaffected, but the AP duration (APD) decreased with increasing frequency. Peak depolarization tended to decrease, but it was only significant at 1.0 Hz. The decrease in APD was not due to frequency-dependent changes in the delayed inward rectifier (IKr) or the transient outward (Ito) current, as neither appeared to be present in varanid ventricular myocytes. Our results suggest that a negative FFR relationship in varanid lizard ventricle is caused by decreased amplitude of the Ca2+transient coupled with an increase in diastolic Ca2+, which leads to incomplete relaxation between beats at high frequencies. This coincides with shortened APD at higher frequencies.