Bell Thomas J, Thaler Christopher, Castiglioni Andrew J, Helton Thomas D, Lipscombe Diane
Department of Neuroscience, Brown University, Providence, RI 02912, USA.
Neuron. 2004 Jan 8;41(1):127-38. doi: 10.1016/s0896-6273(03)00801-8.
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.
N型钙通道对疼痛传导至关重要。这些通道的抑制剂是强效镇痛药，但目前N型阻滞剂的临床应用仍受神经系统其他区域不良作用的限制。我们现在证明，N型通道的一种独特剪接异构体仅局限于背根神经节。通过在单细胞水平上进行功能和分子分析相结合的方法，我们表明背根神经节特异性外显子e37a优先存在于表达伤害性标记物VR1和Na(V)1.8的神经元中所表达的Ca(V)2.2 mRNA中。外显子37a在细胞特异性的包含与伤害性神经元中显著更大的N型电流密切相关。N型通道的这种独特剪接异构体可能代表疼痛治疗的一个新靶点。
