MECHANOTRANSDUCTION IN STRETCH-INDUCED HYPERTROPHY OF CARDIAC MYOCYTES
MECHANOTRANSDUCTION IN STRETCH-INDUCED HYPERTROPHY OF CARDIAC MYOCYTES
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DOI：
10.3109/10799899309073692
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发表时间：
1993-01-01
期刊：
影响因子：
--
通讯作者：
IZUMO, S
中科院分区：
文献类型：
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作者：
SADOSHIMA, J;IZUMO, S
心肌的机械负荷导致许多立即早期（IE）基因的快速激活和肥大。然而，很少有人知道肌肉细胞如何感知机械负荷和调节基因表达。我们研究了几个假定的mechanotransducers在拉伸诱导的心肌细胞肥大的变形硅胶片上生长的作用。使用膜片钳技术，我们发现了一个单一的类拉伸激活的阳离子通道，这是完全和可逆的阻断钆。钆对该通道的抑制不影响拉伸诱导的IE基因表达或肥大。无论是破坏微管与秋水仙素，也不是肌动蛋白微丝细胞松弛素D阻止拉伸诱导的IE基因表达。河豚毒素抑制收缩活动并不影响牵张诱导的IE基因表达或肥大。这些结果表明，拉伸激活的阳离子通道，微管，微丝，和收缩活动不是mechanotransducers。初步结果表明，细胞拉伸可能会导致释放的生长因子（S），这反过来又启动了级联的心肌细胞肥大反应。
Mechanical loading of cardiac muscles causes rapid activation of a number of immediate-early (IE) genes and hypertrophy. However, little is known as to how muscle cells sense mechanical load and regulate gene expression. We examined roles of several putative mechanotransducers in stretch-induced hypertrophy of cardiac myocytes grown on a deformable silicone sheet. Using the patch-clamp technique, we found a single class of stretch-activated cation channels which was completely and reversibly blocked by gadolinium. The inhibition of this channel by gadolinium did not affect either stretch-induced expression of the IE genes or hypertrophy. Neither disruption of microtubules with colchicine nor that of actin microfilaments by cytochalasin D prevented the stretch-induced IE gene expression. Arresting contractile activity by tetrodotoxin did not affect the stretch-induced IE gene expression or hypertrophy. These results suggest that stretch-activated cation channels, microtubules, microfilaments, and contractile activity are not the mechanotransducers. Preliminary results suggest that cell stretch may cause a release of a growth factor(s), which in turn initiates a cascade of hypertrophic response of cardiac myocytes.