Creatine kinase inhibitor iodoacetamide antagonizes calcium-stimulated inotropy in cardiomyocytes.
Creatine kinase inhibitor iodoacetamide antagonizes calcium-stimulated inotropy in cardiomyocytes.
复制标题
肌酸激酶抑制剂碘乙酰胺拮抗心肌细胞中钙刺激的正性肌力。
DOI：
10.1111/j.1440-1681.2008.05034.x
复制
发表时间：
2009
影响因子：
2.9
通讯作者：
Ingwall,JoanneS
中科院分区：
文献类型：
--
作者：
Ren,Jun;Davidoff,AmyJ;Ingwall,JoanneS
1 已知肌酸激酶的抑制会抑制完整心脏的心脏收缩储备，但其根本机制尚未阐明。2本研究旨在检查肌酸激酶抑制引起的心脏抑制是否是由于重要收缩元件（即心肌细胞）水平的作用所致。用肌酸激酶抑制剂碘乙酰胺 (90 µmol/L) 灌注成年大鼠心肌细胞 90 分钟。分别使用边缘检测和荧光显微镜评估机械和细胞内 Ca2+ 特性。肌细胞灌注正常 (1.3 mmol/L) 或高 (3.3 mmol/L) 细胞外 Ca2+ 收缩缓冲液。检查机械功能，包括峰值缩短 (PS)、缩短/再延长的最大速度 (±dL/dt)、达到 90% PS 的时间 (TPS90)、达到 90% 再延长的时间 (TR90) 和缩短/再延长的积分（标准化为 PS）。使用以下指标评估细胞内 Ca2+ 瞬变：fura-2 荧光强度 (ΔFFI) 静息和上升以及细胞内 Ca2+ 衰变时间常数。 3 结果表明，细胞外 Ca2+ 刺激心肌细胞正性肌力升高，表现为 PS、±dL/dt、缩短面积增加、静息 FFI 和 ΔFFI 与缩短的 TR90 和细胞内 Ca2+ 衰变时间常数相关。高细胞外Ca2+不影响TPS90和再延长面积。碘乙酰胺消除了高 Ca2+ 诱导的 PS、±dL/dt、缩短面积、静息 FFI、ΔFFI 的增加，并缩短了 TR90 和细胞内 Ca2+ 衰减时间常数。碘乙酰胺本身显着增强了再延长面积和 TR90，而不影响其他指标。 4总的来说，这些数据表明，肌酸激酶的抑制会减弱细胞外 Ca2+ 诱导的心肌细胞收缩反应（即心脏收缩储备）的增加。
1Inhibition of creatine kinase is known to suppress cardiac contractile reserve in intact hearts, although the underlying mechanism has not been elucidated.2The present study was designed to examine whether cardiac depression induced by creatine kinase inhibition was due to action at the level of the essential contractile element, namely cardiomyocytes. Adult rat cardiomyocytes were perfused with the creatine kinase inhibitor iodoacetamide (90 µmol/L) for 90 min. Mechanical and intracellular Ca2+properties were evaluated using edge‐detection and fluorescence microscopy, respectively. Myocytes were superfused with normal (1.3 mmol/L) or high (3.3 mmol/L) extracellular Ca2+contractile buffer. Mechanical function was examined, including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time to 90% PS (TPS90), time to 90% relengthening (TR90) and integration of shortening/relengthening (normalized to PS). Intracellular Ca2+transients were evaluated using the following indices: resting and rise of fura‐2 fluorescence intensity (ΔFFI) and intracellular Ca2+decay time constant.3The results indicate that elevated extracellular Ca2+stimulated cardiomyocyte positive inotrope, manifested as increased PS, ±dL/dt, area of shortening, resting FFI and ΔFFI associated with a shortened TR90and intracellular Ca2+decay time constant. High extracellular Ca2+did not affect TPS90and area of relengthening. Iodoacetamide ablated high Ca2+‐induced increases in PS, ±dL/dt, area of shortening, resting FFI, ΔFFI and shortened TR90and intracellular Ca2+decay time constant. Iodoacetamide itself significantly enhanced the area of relengthening and TR90without affecting other indices.4Collectively, these data demonstrate that inhibition of creatine kinase blunts high extracellular Ca2+‐induced increases in cardiomyocyte contractile response (i.e. cardiac contractile reserve).