Tang L, Gao W, Taylor P B
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6059, USA.
Eur J Pharmacol. 1996 Dec 30;318(2-3):349-56. doi: 10.1016/s0014-2999(96)00805-9.
Rate-dependent force production was investigated using small trabecular muscle from control and hypertrophied rat cardiac muscle. Cardiac hypertrophy was induced by daily subcutaneous injection of isoproterenol (0.3 mg/kg body weight) for 12 days. The force-frequency relationship, for the control rat myocardium, is clearly biphasic. A stepped increase in stimulation frequency from 0.1 to 0.5 Hz results in a decrease in contractile force (negative phase). However, at higher stimulation frequency above 0.5 Hz, an increased contractile force is revealed (positive phase). Membrane action potential duration (APD50) was used to reflect sarcolemmal Ca2+ influx. The frequency-dependent increase in APD50 and the ability of nifedipine, a sarcolemmal L-type Ca2+ channel blocker, to eliminate the positive-force frequency response, indicate that sarcolemmal Ca2+ influx is important for force development at high stimulation frequency. Relative Ca2+ content of sarcoplasmic reticulum is estimated from rapid cooling contractures. The parallel change of rapid cooling contractures and twitch force suggests that the sarcoplasmic reticulum Ca2+ content alters with varying frequencies of stimulation. Isoproterenol-induced hypertrophied muscle shows a greater contractile force, increased nifedipine-sensitive force development and prolonged APD50 compared to controls. These data suggest a greater availability of intracellular Ca2+ to activate contraction in hypertrophied muscle, possibly by amplified Ca2+ influx via L-type channel.
利用对照大鼠和肥大大鼠心肌的小梁小肌研究了速率依赖性力的产生。通过每日皮下注射异丙肾上腺素（0.3mg/kg体重）持续12天诱导心脏肥大。对于对照大鼠心肌，力-频率关系明显呈双相性。刺激频率从0.1Hz逐步增加到0.5Hz会导致收缩力降低（负相）。然而，在高于0.5Hz的较高刺激频率下，收缩力会增加（正相）。膜动作电位持续时间（APD50）用于反映肌膜Ca2+内流。APD50随频率的增加以及肌膜L型Ca2+通道阻滞剂硝苯地平消除正向力频率反应的能力，表明肌膜Ca2+内流对于高刺激频率下的力发展很重要。通过快速冷却挛缩来估计肌浆网的相对Ca2+含量。快速冷却挛缩和抽搐力的平行变化表明肌浆网Ca2+含量随刺激频率的变化而改变。与对照相比，异丙肾上腺素诱导的肥大肌肉表现出更大的收缩力、增加的硝苯地平敏感性力发展以及延长的APD50。这些数据表明肥大肌肉中细胞内Ca2+激活收缩的可用性更高，可能是通过L型通道放大的Ca2+内流实现的。
