NHE-1 blockade reversed changes in calcium transient in myocardial slices from isoproterenol-induced hypertrophied rat left ventricle
NHE-1 blockade reversed changes in calcium transient in myocardial slices from isoproterenol-induced hypertrophied rat left ventricle
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NHE-1阻断逆转了异丙肾上腺素诱导的肥大大鼠左心室心肌切片中钙瞬变的变化
DOI：
10.1016/j.bbrc.2012.02.041
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发表时间：
2012
期刊：
影响因子：
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他
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作者：
Hattori H;Obata K;Takaki M;他
我们以前报道过，异丙肾上腺素（ISO）诱导的肥大大鼠心脏的左心室（LV）切片显示，由于兴奋-收缩偶联中Ca 2+处理的重塑，能量消耗增加，即，抑制SERCA 2a活性，增强Na+/Ca ~（2+）交换器-1（NCX-1）活性。Na+/H+交换器-1（NHE-1）抑制剂（NHEI）已被证明在心脏重塑的发展中发挥有益作用。我们假设一种新的NHE-1选择性抑制剂BIIB 723通过抑制NCX-1活性来阻止ISO诱导的肥大大鼠心脏LV切片中Ca 2+处理的重塑。ISO组多细胞Ca 2+瞬变持续时间的显著缩短在ISO+ BIIB 723组中恢复正常。ISO+ BIIB 723组中ISO组在高[Ca 2 +] o LV切片处产生的多细胞Ca 2+波（CaW）振幅的显著增加也正常化。然而，增强的NCX-1活性不被BIIB 723拮抗。我们最近报道了ISO诱导的钙处理蛋白SERCA 2a的下调通过BIIB 723进行了正常化。因此，BIIB 723可能通过SERCA 2a活性的正常化缩短了LV切片中多细胞Ca 2+瞬时持续时间并增加了CaW振幅。此外，本研究结果提示，LV切片中的多细胞Ca 2+瞬变持续时间和CaW幅度可能比SERCA 2a蛋白表达水平更好地反映SERCA 2a活性。
We previously reported that left ventricular (LV) slices from isoproterenol (ISO)-induced hypertrophied rat hearts showed an increase of energy expenditure due to remodeling of Ca2+handling in excitation–contraction coupling, i.e., suppressed SERCA2a activity and enhanced Na+/Ca2+exchanger-1 (NCX-1) activity. Na+/H+exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated to exert beneficial effects in the development of cardiac remodeling. We hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling of Ca2+handling in LV slices of ISO-induced hypertrophied rat hearts mediated by inhibiting NCX-1 activity. The significant shortening in duration of multi-cellular Ca2+transient in ISO group was normalized in ISO+BIIB723 group. The significant increase in amplitude of multi-cellular Ca2+waves (CaW) generated at high [Ca2+]oof LV slices in ISO group was also normalized in ISO+BIIB723 group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We recently reported that ISO-induced down-regulation of a Ca2+handling protein, SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723 normalized shortened multi-cellular Ca2+transient duration and increased CaW amplitude in LV slices mediated via normalization of SERCA2a activity. Furthermore, the results presented here suggest the multi-cellular Ca2+transient duration and CaW amplitude in LV slices might be better indices reflecting SERCA2a activity than SERCA2a protein expression level.