Cell-specific alternative splicing increases calcium channel current density in the pain pathway
Cell-specific alternative splicing increases calcium channel current density in the pain pathway
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DOI：
10.1016/s0896-6273(03)00801-8
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发表时间：
2004-01-08
期刊：
影响因子：
16.2
通讯作者：
Lipscombe, D
中科院分区：
文献类型：
--
作者：
Bell, TJ;Thaler, C;Lipscombe, D
N型钙通道在痛觉传导中起着重要作用。这些通道的抑制剂是强效镇痛剂，但目前N型阻滞剂的临床使用仍然受到神经系统其他区域不良作用的限制。我们现在证明，一个独特的剪接亚型的N-型通道仅限于背根神经节。通过在单细胞水平上的功能和分子分析的组合，我们表明DRG特异性外显子e37 a优先存在于含有伤害性标记物VR 1和Na（V）1.8的神经元中表达的Ca（V）2.2 mRNA中。细胞特异性包含外显子37 a与伤害性神经元中显著更大的N型电流密切相关。这种独特的剪接亚型的N型通道可能代表一个新的目标疼痛管理。
N-type calcium channels are critical for pain transduction. Inhibitors of these channels are powerful analgesics, but clinical use of current N-type blockers; remains limited by undesirable actions in other regions of the nervous system. We now demonstrate that a unique splice isoform of the N-type channel is restricted exclusively to dorsal root ganglia. By a combination of functional and molecular analyses at the single-cell level, we show that the DRG-specific exon, e37a, is preferentially present in Ca(V)2.2 mRNAs expressed in neurons that contain nociceptive markers, VR1 and Na(V)1.8. Cell-specific inclusion of exon 37a correlates closely with significantly larger N-type currents in nociceptive neurons. This unique splice isoform of the N-type channel could represent a novel target for pain management.