Pathophysiological significance of T-type Ca2+ channels: expression of T-type Ca2+ channels in fetal and diseased heart.
Pathophysiological significance of T-type Ca2+ channels: expression of T-type Ca2+ channels in fetal and diseased heart.
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DOI：
10.1254/jphs.fmj05002x3
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发表时间：
2005
影响因子：
3.5
通讯作者：
K. Yasui;Noriko Niwa;Haruki Takemura;T. Opthof;Takao Muto;M. Horiba;A. Shimizu;Jong‐Kook Lee;H. Honjo;K. Kamiya;I. Kodama
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文献类型：
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作者：
K. Yasui;Noriko Niwa;Haruki Takemura;T. Opthof;Takao Muto;M. Horiba;A. Shimizu;Jong‐Kook Lee;H. Honjo;K. Kamiya;I. Kodama
胎儿基因的重新表达被认为是患病心脏离子重塑的基础。据报道，t型Ca（2+）通道在胚胎心脏中有功能表达。本文采用膜片钳和定量PCR技术，总结了小鼠脑室t型Ca（2+）通道从性交后9.5天到成年期的发育变化。此外，我们还在心肌梗死（MI）和主动脉束带（AOB）引起的肥厚心室中引入了t型Ca（2+）通道的表达。大量的t型Ca（2+）通道电流记录在9.5和18 dpc。低浓度的Ni（2+）对电流有抑制作用。在成虫期检测不到电流。Ca(v)3.2 (α (1H)) mRNA在9.5和18 dpc时主要表达。Ca(v)3.1 （α (1G)）从9.5增加到18 dpc，但与Ca(v)3.2相比仍处于较低水平。成虫期Ca(v)3.1大于Ca(v)3.2。在心肌梗死中，Ca(v)3.1 mRNA与脑钠肽（BNP） mRNA呈负相关，而Ca(v)3.2 mRNA与BNP mRNA呈正相关。在AOB中，这些相关性很弱。我们还分析了这些心脏中的神经元限制性沉默因子（NRSF），因为它是胎儿心脏基因程序转录的抑制因子。心肌梗死患者NRSF与BNP的负相关强于AOB患者。我们的研究结果表明，Ca(v)3.2是胚胎心脏功能t型Ca（2+）通道的基础，并提示NRSF可能调节病变心脏中Ca(v)3.2的表达。
Re-expression of fetal genes has been considered to underlie ionic remodeling in diseased heart. T-type Ca(2+) channels have been reported to be functionally expressed in embryonic hearts. In this review, we summarize developmental changes of T-type Ca(2+) channels in mouse ventricles from 9.5 days postcoitum (dpc) to adulthood, using patch clamp and quantitative PCR. In addition, we introduced T-type Ca(2+) channel expression in hypertrophied ventricles caused by myocardial infarction (MI) and aortic banding (AOB). Substantial T-type Ca(2+) channel current was recorded at both 9.5 and 18 dpc. The currents were inhibited by Ni(2+) at low concentrations. The current was not detectable in the adult stage. Ca(v)3.2 (alpha(1H)) mRNA is expressed dominantly at both 9.5 and 18 dpc. Ca(v)3.1 (alpha(1G)) increases from 9.5 to 18 dpc, but remains at low level compared with Ca(v)3.2. In contrast, Ca(v)3.1 is greater than Ca(v)3.2 at the adult stage. In MI, Ca(v)3.1 mRNA correlates negatively with brain natriuretic peptide (BNP) mRNA, whereas Ca(v)3.2 mRNA correlates positively with BNP mRNA. In AOB, these correlations are weak. We also analyzed the neuron-restrictive silencer factor (NRSF) in these hearts because it is the suppressor of transcription of the fetal cardiac gene program. The negative correlation between NRSF and BNP was stronger in MI than in AOB. Our findings show that Ca(v)3.2 underlies the functional T-type Ca(2+) channel in embryonic heart and suggest that NRSF may regulate Ca(v)3.2 expression in diseased hearts.