DIFFERENTIAL PHOSPHOLAMBAN GENE-EXPRESSION IN MURINE CARDIAC COMPARTMENTS - MOLECULAR AND PHYSIOLOGICAL ANALYSES
DIFFERENTIAL PHOSPHOLAMBAN GENE-EXPRESSION IN MURINE CARDIAC COMPARTMENTS - MOLECULAR AND PHYSIOLOGICAL ANALYSES
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DOI：
10.1161/01.res.77.2.342
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发表时间：
1995-08-01
影响因子：
20.1
通讯作者：
KRANIAS, EG
中科院分区：
文献类型：
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作者：
KOSS, KL;PONNIAH, S;KRANIAS, EG
受磷蛋白是心肌肌浆网中钙泵的调节因子，在小鼠心房和心室肌之间差异表达。从心房瓣和心室尖分离的RNA的定量分析表明，受磷蛋白基因转录本拷贝数在心室中比FVB/N小鼠的心房高2.5倍，在心室中比B6 D2/F1小鼠品系的心房高6倍。这些发现证实了原位杂交研究的心肺切片从两种小鼠菌株，和受磷蛋白转录本也观察到肺心肌的两种菌株。相对于α-肌球蛋白重链（α-MHC）的受磷蛋白转录物水平的分析揭示了与FVB/N鼠品系的心房相比，心室中的受磷蛋白丰度高3倍。然而，心室中Ca 2 +-ATPase的相对mRNA水平（肌浆网Ca 2 +-ATPase [SERCA 2]与α-MHC的比率）是心房中的80%。因此，受磷蛋白与SERCA 2 mRNA的相对比率在心房中比在心室中低4.7倍。心房中受磷蛋白与SERCA 2的较低转录比与显著缩短的半松弛时间相关（心房为17.40+/-0.71毫秒，心室为30.58+/-2.04毫秒），在最大长度张力下记录的离体灌流心脏组织制备物中进行评估。收缩时间，测量为达到峰值张力的时间，在相同的组织制备物中，与心室肌（44.60+/-2.55毫秒）相比，心房肌（27.36+/-0.82毫秒）也显著缩短。这些研究结果表明，受磷蛋白基因表达差异调节小鼠心房和心室肌，这种差异表达可能与这些心脏室的收缩参数的差异。
Phospholamban, the regulator of the Ca2+ pump in cardiac sarcoplasmic reticulum, is differentially expressed between murine atrial and ventricular muscles. Quantitative analyses of RNA isolated from atrial flaps and ventricular apices indicated that the phospholamban gene transcript copy number is 2.5-fold higher in the ventricle compared with the atrium of the FVB/N mouse and 6-fold higher in the ventricle compared with the atrium of the B6D2/F1 mouse strain. These findings were corroborated by in situ hybridization studies of cardiopulmonary sections from both murine strains, and phospholamban transcripts were also observed in pulmonary myocardia of both strains. Analyses of phospholamban transcript levels relative to alpha-myosin heavy chain (alpha-MHC) revealed a 3-fold higher phospholamban abundance in the ventricle compared with the atrium of the FVB/N murine strain. However, the relative mRNA level of Ca2+-ATPase (ratio of sarcoplasmic reticulum Ca2+-ATPase [SERCA2] to alpha-MHC) in the ventricle was 80% of that in the atrium. Consequently, the relative ratio of phospholamban to SERCA2 mRNA was 4.7-fold lower in the atrium than in the ventricle. The lower transcript ratio of phospholamban to SERCA2 in the atrium was associated with significantly shortened times to half-relaxation (17.40+/-0.71 milliseconds for atrium versus 30.58+/-2.04 milliseconds for ventricle), assessed in isolated superfused cardiac tissue preparations recorded at maximum length tension Contraction times, measured as times to peak tension, were also significantly shortened in atrial muscle (27.36+/-0.82 milliseconds) compared with ventricular muscle (44.60+/-2.55 milliseconds), assessed in the same tissue preparations. These findings suggest that phospholamban gene expression is differentially regulated in murine atrial and ventricular muscles and that this differential expression may be associated with differences in the contractile parameters of these cardiac compartments.