Antisense oligonucleotides against rat brain alpha1E DNA and its atrial homologue decrease T-type calcium current in atrial myocytes.
Antisense oligonucleotides against rat brain alpha1E DNA and its atrial homologue decrease T-type calcium current in atrial myocytes.
复制标题
针对大鼠脑 alpha1E DNA 及其心房同源物的反义寡核苷酸可降低心房肌细胞中的 T 型钙电流。
DOI：
10.1073/pnas.94.26.14936
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发表时间：
1997
影响因子：
11.1
通讯作者：
Best,PM
中科院分区：
文献类型：
--
作者：
Piedras-Rentería,ES;Chen,CC;Best,PM
低电压激活的或T型钙电流是神经元和肌肉兴奋性、分泌以及可能的细胞生长和分化的重要调节剂。编码低电压激活通道蛋白的孔形成亚基的基因（或多个基因）尚未明确鉴定。我们已经使用逆转录-PCR，以确定部分克隆大鼠心房肌细胞，共享高同源性的E类钙通道基因的成员。针对这些部分克隆之一（raE 1）的反义寡核苷酸特异性地阻断T-电流密度的增加，这通常是当心房肌细胞用胰岛素样生长因子1（IGF-1）处理时产生的。靶向神经元大鼠α 1 E序列部分的反义寡核苷酸也阻断了IGF-1诱导的T电流增加，这表明部分克隆中与α 1 E的高度同源性可能存在于完整的心房序列中。在这些细胞中表达的基础T电流也被反义寡核苷酸阻断，这与IGF-1上调编码基础电流的相同基因的观点一致。这些结果支持了这样的假设，即E类钙通道基因的成员编码心房肌细胞中的低电压激活的钙通道。
Low voltage-activated, or T-type, calcium currents are important regulators of neuronal and muscle excitability, secretion, and possibly cell growth and differentiation. The gene (or genes) coding for the pore-forming subunit of low voltage-activated channel proteins has not been unequivocally identified. We have used reverse transcription–PCR to identify partial clones from rat atrial myocytes that share high homology with a member of the E class of calcium channel genes. Antisense oligonucleotides targeting one of these partial clones (raE1) specifically block the increase in T-current density that normally results when atrial myocytes are treated with insulin-like growth factor 1 (IGF-1). Antisense oligonucleotides targeting portions of the neuronal rat α1Esequence, which are not part of the clones detected in atrial tissue, also block the IGF-1-induced increase in T-current, suggesting that the high homology to α1Eseen in the partial clone may be present in the complete atrial sequence. The basal T-current expressed in these cells is also blocked by antisense oligonucleotides, which is consistent with the notion that IGF-1 up-regulates the same gene that encodes the basal current. These results support the hypothesis that a member of the E class of calcium channel genes encodes a low voltage-activated calcium channel in atrial myocytes.