REDUCED CALCIUM CURRENT-DENSITY IN SINGLE MYOCYTES ISOLATED FROM HYPERTROPHIED FAILING GUINEA-PIG HEARTS
REDUCED CALCIUM CURRENT-DENSITY IN SINGLE MYOCYTES ISOLATED FROM HYPERTROPHIED FAILING GUINEA-PIG HEARTS
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DOI：
10.1006/jmcc.1994.1132
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发表时间：
1994-09-01
影响因子：
5
通讯作者：
ARONSON, RS
中科院分区：
文献类型：
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作者：
MING, Z;NORDIN, C;ARONSON, RS
本研究探讨了跨膜钙电流（i - ca）改变的可能性，通过其调节肌浆网Ca2+释放的能力，可能有助于降低峰值[Ca2+](i)，我们之前在肥厚性衰竭心肌中观察到。采用全细胞膜片钳测量从正常豚鼠心脏分离的单个豚鼠心室肌细胞中的I-Ca，以及从幼龄动物升主动脉带后逐渐发展的左心室压力过载诱导肥厚和衰竭的豚鼠心脏中分离的心室肌细胞。在肥厚性衰竭心脏的肌细胞中，膜电容（C-m）显著增加，I-Ca （C-m归一化）显著降低。肥厚性衰竭心脏的肌细胞在I-Ca的激活变量(d)的电压依赖性（-30 mV除外）、I-Ca失活的去除时间过程和I-Ca衰变的时间常数方面与正常肌细胞没有显著差异。对I-Ca失活变量(f)的电压依赖性测量表明，肥厚性衰竭心脏的肌细胞在0、-10和-20 mV时存在更多的稳态失活。所有数据的多元回归分析表明，与肥厚和心力衰竭的任何特定影响无关，I-Ca密度随心肌细胞膜面积的增加而降低（由C-m反映）。我们得出结论，从肥厚性衰竭心脏分离的肌细胞中，I-Ca （C-m的标准化）显著降低，可能是通过细胞大小增加的过程本身。
The present study explored the possibility that an alteration in the transmembrane calcium current (I-Ca), through its ability to modulate Ca2+ release from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca2+](i) we previously observed in hypertrophied failing myocardium. Whole-cell patch clamp was used to measure I-Ca in single guinea pig ventricular myocytes isolated from hearts of normal guinea pigs and from guinea pig hearts in which hypertrophy and failure were induced by gradually developing left ventricular pressure overload subsequent to ascending aortic banding of young animals. Membrane capacitance (C-m) was significantly greater, and I-Ca, normalized for C-m, was significantly lower in myocytes from hypertrophied failing hearts. Myocytes from hypertrophied failing hearts did not differ significantly from normal myocytes in terms of the voltage-dependence of the activation variable (d) of I-Ca (except at -30 mV), the time course of removal of inactivation of I-Ca, and the time constant of decay of I-Ca. Measurement of the voltage dependence of the inactivation Variable (f) of I-Ca showed that significantly more steady-state inactivation was present at 0, -10, and -20 mV in myocytes from hypertrophied failing hearts. Multiple regression analysis of all data indicated that I-Ca density decreased with increasing myocyte membrane area (as reflected by C-m) irrespective of any specific effects of hypertrophy and heart failure. We conclude that I-Ca, normalized for C-m, is significantly reduced in myocytes isolated from hypertrophied failing hearts, probably by a process associated with increased cell size, per se.