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Role of protein phosphatases in regulation of cardiac inotropy and relaxation.

机译:蛋白质磷酸酶在调节心脏肌力和放松中的作用。

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摘要

We studied the effects of the protein phosphatase (PP) inhibitor cantharidin (Cant) on time parameters and force of contraction (FOC) in isometrically contracting electrically driven guinea pig papillary muscles. We correlated the mechanical parameters of contractility with phosphorylation of the inhibitory subunit of troponin (TnI-P) and with the site-specific phosphorylation of phospholamban (PLB) at serine-16 (PLB-Ser-16) and threonine-17 (PLB-Thr-17). Cant (after 30 min) started to increase FOC (112 +/- 4% of control, n = 10) and TnI-P and PLB-Thr-17 (120 +/- 5 and 128 +/- 7% of control) without any alteration of relaxation time. Cant (10 microM) started to increase PLB-Ser-16, but the relaxation was shortened at only 100 microM (from 140 +/- 9 to 116 +/- 12 ms, n = 9). Moreover, 100 microM Cant, 3 min after application, started to increase PLB-Thr-17, TnI-P, and FOC. Cant (100 microM) began to increase PLB-Ser-16 after 20 min. This was accompanied by shortening of relaxation time. Differences in protein kinase activation or different substrate specificities of PP may explain the difference in Cant-induced site-specific phosphorylation of PLB in isometrically contracting papillary muscles. Moreover, PLB-Thr-17 may be important for inotropy, whereas PLB-Ser-16 could be a major determinant of relaxation time.
机译:我们研究了等轴收缩电动豚鼠乳头肌中蛋白质磷酸酶(PP)抑制剂cantharidin(Cant)对时间参数和收缩力(FOC)的影响。我们将收缩力的机械参数与肌钙蛋白抑制亚基(TnI-P)的磷酸化以及磷酸丝蛋白(PLB)在丝氨酸16(PLB-Ser-16)和苏氨酸17(PLB- Thr-17)。 Cant(30分钟后)开始增加FOC(对照组的112 +/- 4%,n = 10)和TnI-P和PLB-Thr-17(对照组的120 +/- 5和128 +/- 7%)无需改变放松时间。斜率(10 microM)开始增加PLB-Ser-16,但松弛仅在100 microM时被缩短(从140 +/- 9到116 +/- 12 ms,n = 9)。此外,在施用后3分钟,100 microM Cant开始增加PLB-Thr-17,TnI-P和FOC。 20分钟后,Cant(100 microM)开始增加PLB-Ser-16。这伴随着放松时间的缩短。蛋白激酶激活的差异或PP的不同底物特异性可能解释了等轴收缩乳头肌中Cant诱导的PLB的位点特异性磷酸化的差异。此外,PLB-Thr-17对于正性肌力可能很重要,而PLB-Ser-16可能是松弛时间的主要决定因素。

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