Spinale F G, Tempel G E, Mukherjee R, Eble D M, Brown R, Vacchiano C A, Zile M R
Medical University of South Carolina, Charleston 29425.
Cardiovasc Res. 1994 Aug;28(8):1243-50. doi: 10.1093/cvr/28.8.1243.
The aim was to examine the relationship between changes in myocyte function to changes in protein and mRNA content of components of the beta adrenergic system with tachycardia induced cardiomyopathy.
Contractile function and beta adrenergic responsiveness were measured in isolated myocytes from control pigs (n = 6) and in pigs subjected to three weeks of pacing induced supraventricular tachycardia (n = 6). beta Receptor density and affinity, the relative content of the stimulatory (Gs) and inhibitory (Gi) subunits of the G protein complex, and adenylate cyclase activity were determined from sarcolemmal preparations. In order to determine whether these changes were accompanied by alterations in steady state mRNA levels for specific components of the beta adrenergic system, mRNA content for the beta 1 adrenergic receptor and the G alpha s and G alpha i2 subunits of the G protein complex was measured.
Chronic supraventricular tachycardia caused a 36% increase in left ventricular end diastolic dimension and a 61% decrease in left ventricular fractional shortening compared to controls. The velocity of isolated myocyte shortening was 50% lower in myocytes from hearts with tachycardia cardiomyopathy than in control myocytes. In the presence of 50 nM isoprenaline or 2 microM forskolin, the velocity of myocyte shortening was 65% lower in the myopathic myocytes than in the controls. With the development of tachycardic cardiomyopathy, beta adrenergic receptor density fell by 25% with no change in affinity, Gs decreased by 35%, and Gi increased by over 50% compared to controls. Basal adenylate cyclase activity and isoprenaline and forskolin stimulated adenylate cyclase activity fell by over 50% with supraventricular tachycardia compared to controls. The relative content of G alpha i2 mRNA increased threefold with the development of tachycardic cardiomyopathy with no change in the relative abundance of mRNA for the beta 1 receptor or G alpha s when compared with controls.
The changes in myocyte beta adrenergic responsiveness with the development of tachycardic cardiomyopathy are due to alterations in cellular mechanisms (decreased beta receptor and Gs density, increased Gi) and in molecular mechanisms (increased Gi mRNA content).
研究心动过速性心肌病中，心肌细胞功能变化与β肾上腺素能系统各组分蛋白质及mRNA含量变化之间的关系。
在对照猪（n = 6）及经历三周起搏诱导的室上性心动过速的猪（n = 6）的分离心肌细胞中，测量收缩功能及β肾上腺素能反应性。从肌膜制备物中测定β受体密度及亲和力、G蛋白复合物刺激性（Gs）和抑制性（Gi）亚基的相对含量以及腺苷酸环化酶活性。为了确定这些变化是否伴随着β肾上腺素能系统特定组分的稳态mRNA水平改变，测量β1肾上腺素能受体、G蛋白复合物的Gαs和Gαi2亚基的mRNA含量。
与对照组相比，慢性室上性心动过速使左心室舒张末期内径增加36%，左心室缩短分数降低61%。心动过速性心肌病心脏的心肌细胞中，分离的心肌细胞缩短速度比对照心肌细胞低50%。在存在50 nM异丙肾上腺素或2 μM福斯可林的情况下，病变心肌细胞的心肌细胞缩短速度比对照组低65%。随着心动过速性心肌病的发展，与对照组相比，β肾上腺素能受体密度下降25%，亲和力无变化，Gs下降35%，Gi增加超过50%。与对照组相比，室上性心动过速时基础腺苷酸环化酶活性以及异丙肾上腺素和福斯可林刺激的腺苷酸环化酶活性下降超过50%。与对照组相比，随着心动过速性心肌病的发展，Gαi2 mRNA的相对含量增加了三倍，β1受体或Gαs的mRNA相对丰度无变化。
心动过速性心肌病发展过程中心肌细胞β肾上腺素能反应性的变化是由于细胞机制改变（β受体和Gs密度降低、Gi增加）以及分子机制改变（Gi mRNA含量增加）所致。
