Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate.
Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2+ spark rate.
复制标题
DOI：
10.1161/circresaha.108.193334
复制
发表时间：
2009-03-27
影响因子：
20.1
通讯作者：
Kohl P
中科院分区：
文献类型：
--
作者：
Iribe G;Ward CW;Camelliti P;Bollensdorff C;Mason F;Burton RA;Garny A;Morphew MK;Hoenger A;Lederer WJ;Kohl P
我们研究了碳纤维 (CF) 施加的轴向拉伸对大鼠离体心肌细胞舒张期 Ca2+ 火花率的急性影响。 CF 要么附着在细胞两端（以最大化拉伸区域），要么附着在细胞的中心和一端（以比较拉伸和未拉伸半电池的响应）。拉伸细胞部分中的肌节长度增加了 8.01 ± 0.94%，并记录 XY 共焦图像的时间序列以监测舒张期 Ca2+ 火花频率和动态。全细胞拉伸导致 Ca2± 火花率在 5 秒内急剧增加（至 130.7 ± 6.4%），随后在持续扩张的 1 分钟内返回到接近背景水平（至 104.4±5.1%）。火花率仅在拉伸单元区域增加，拉伸和非拉伸区域中火花幅度、达到峰值的时间和衰减时间常数没有显着差异。阻断拉伸激活的离子通道（2 gmol/L GsMTx-4）、灌注不含 Na±/Ca2+ 的溶液和阻断一氧化氮合成（1 mmol/L L-NAME）均对拉伸引起的 Ca2± 火花率急剧增加没有影响。相反，干扰细胞骨架完整性（10 gmol/L 秋水仙碱 2 小时）会消除反应。随后的电子显微镜断层扫描证实微管与 T 管-肌浆网复合体非常接近（在·10−8m 以内）。总之，大鼠心肌细胞的轴向拉伸通过一种独立于肌膜拉伸激活的离子通道、一氧化氮合成或细胞外钙的可用性但需要细胞骨架完整性的机制，急剧而短暂地增加了肌浆网 Ca2+ 放电率。微管介导的兰尼碱受体功能调节的潜力值得进一步研究。
We investigate acute effects of axial stretch, applied by carbon fibers (CFs), on diastolic Ca2± spark rate in rat isolated cardiomyocytes. CFs were attached either to both cell ends (to maximize the stretched region), or to the center and one end of the cell (to compare responses in stretched and nonstretched half-cells). Sarcomere length was increased by 8.01 ± 0.94% in the stretched cell fraction, and time series of XY confocal images were recorded to monitor diastolic Ca2± spark frequency and dynamics. Whole-cell stretch causes an acute increase of Ca2± spark rate (to 130.7 ± 6.4%) within 5 seconds, followed by a return to near background levels (to 104.4±5.1%) within 1 minute of sustained distension. Spark rate increased only in the stretched cell region, without significant differences in spark amplitude, time to peak, and decay time constants of sparks in stretched and nonstretched areas. Block of stretch-activated ion channels (2 gmol/L GsMTx-4), perfusion with Na±/Ca2±-free solution, and block of nitric oxide synthesis (1 mmol/L L-NAME) all had no effect on the stretch-induced acute increase in Ca2± spark rate. Conversely, interference with cytoskeletal integrity (2 hours of 10 gmol/L colchicine) abolished the response. Subsequent electron microscopic tomography confirmed the close approximation of microtubules with the T-tubular–sarcoplasmic reticulum complex (to within · 10−8m). In conclusion, axial stretch of rat cardiomyocytes acutely and transiently increases sarcoplasmic reticulum Ca2± spark rate via a mechanism that is independent of sarcolemmal stretch-activated ion channels, nitric oxide synthesis, or availability of extracellular calcium but that requires cytoskeletal integrity. The potential of microtubule-mediated modulation of ryanodine receptor function warrants further investigation.