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首页> 外文期刊>American Journal of Physiology >Contractile activity is required for sarcomeric assembly in phenylephrine-induced cardiac myocyte hypertrophy.
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Contractile activity is required for sarcomeric assembly in phenylephrine-induced cardiac myocyte hypertrophy.

机译：苯肾上腺素诱导的心肌肥大中肌节组装需要收缩活性。

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摘要

Agonist-induced hypertrophy of cultured neonatal rat ventricular myocytes (NRVM) has been attributed to biochemical signals generated during receptor activation. However, NRVM hypertrophy can also be induced by spontaneous or electrically stimulated contractile activity in the absence of exogenous neurohormonal stimuli. Using single-cell imaging of fura 2-loaded myocytes, we found that low-density, noncontracting NRVM begin to generate intracellular Ca2+ concentration ([Ca2+]i) transients and contractile activity within minutes of exposure to the alpha 1-adrenergic agonist phenylephrine (PE; 50 microM). However, NRVM pretreated with verapamil and then stimulated with PE failed to elicit [Ca2+]i transients and beating. We therefore examined whether PE-induced [Ca2+]i transients and contractile activity were required to elicit specific aspects of the hypertrophic phenotype. PE treatment (48-72 h) increased cell size, total protein content, total protein-to-DNA ratio, and myosin heavy chain (MHC) isoenzyme content. PE also stimulated sarcomeric protein assembly and prolonged MHC half-life. However, blockade of voltage-gated L-type Ca2+ channels with verapamil, diltiazem, or nifedipine (10 microM) blocked PE-induced total protein and MHC accumulation and prevented the time-dependent assembly of myofibrillar proteins into sarcomeres. Inhibition of actin-myosin cross-bridge cycling with 2,3-butanedione monoxime (7.5 mM) also prevented PE-induced total protein and MHC accumulation, indicating that mechanical activity, rather than [Ca2+]i transients per se, was required. In contrast, blockade of [Ca2+]i transients and contractile activity did not prevent the PE-induced increase in cell surface area, activation of the mitogen-activated protein kinases ERK1 and ERK2, or upregulation of atrial natriuretic factor gene expression. Thus contractile activity is required to elicit some but not all aspects of the the hypertrophic phenotype induced by alpha 1-adrenergic receptor activation.
机译：激动剂诱导的培养的新生大鼠心室肌细胞（NRVM）肥大已归因于受体激活过程中产生的生化信号。但是，在没有外源性神经激素刺激的情况下，NRVM肥大也可通过自发或电刺激的收缩活动诱发。使用呋喃2加载的心肌细胞的单细胞成像，我们发现低密度，无收缩的NRVM在暴露于α1-肾上腺素能激动剂去氧肾上腺素（ PE; 50 microM）。然而，NRVM用维拉帕米预处理，然后用PE刺激未能引起[Ca2 +] i瞬变和跳动。因此，我们检查了是否需要PE诱导的[Ca2 +] i瞬变和收缩活性来诱发肥大表型的特定方面。 PE处理（48-72 h）增加了细胞大小，总蛋白含量，总蛋白与DNA的比率以及肌球蛋白重链（MHC）同工酶的含量。 PE还刺激肌节蛋白装配并延长MHC半衰期。但是，用维拉帕米，地尔硫卓或硝苯地平（10 microM）阻断电压门控的L型Ca2 +通道可阻断PE诱导的总蛋白和MHC积累，并阻止肌原纤维蛋白随时间变化组装成肉瘤。用2,3-丁二酮单肟（7.5 mM）抑制肌动蛋白-肌球蛋白跨桥循环也可以防止PE诱导的总蛋白和MHC积累，这表明需要机械活性本身，而不是[Ca2 +] i瞬态。相反，阻断[Ca2 +] i瞬变和收缩活性并不能阻止PE诱导的细胞表面积增加，丝裂原活化蛋白激酶ERK1和ERK2的激活或心钠素基因表达的上调。因此，需要收缩活性来引起由α1-肾上腺素能受体活化诱导的肥大表型的一些但不是全部方面。

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