Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Neuroscience. 2013 Feb 12;231:305-14. doi: 10.1016/j.neuroscience.2012.11.053. Epub 2012 Dec 7.
Neurons within the superficial dorsal horn (SDH) of the rodent spinal cord exhibit distinct firing properties during early life. While this may reflect a unique combination of voltage-gated Na(+) (Na(v)) and voltage-independent (i.e. "leak'') K(+) channels which strongly influence neuronal excitability across the CNS, surprisingly little is known about which genes encoding for Na(v) and leak K(+) channels are expressed within developing spinal pain circuits. The goal of the present study was therefore to characterize the transcriptional expression of these channels within the rat SDH at postnatal days (P) 3, 10, 21 or adulthood using quantitative real-time polymerase chain reaction. The results demonstrate that Na(v) isoforms are developmentally regulated at the mRNA level in a subtype-specific manner, as Na(v)1.2 and Na(v)1.3 decreased significantly from P3 to adulthood, while Na(v)1.1 was up-regulated during this period. The data also indicate selective, age-dependent changes in the mRNA expression of two-pore domain (K(2P)) K(+) channels, as TWIK-related acid-sensitive K(+) channels TASK-1 (KCNK3) and TASK-3 (KCNK9) were down-regulated during postnatal development in the absence of any changes in the tandem of pore domains in a weak inward rectifying K(+) channel (TWIK) isoforms examined (KCNK1 and KCNK6). In addition, a developmental shift occurred within the TREK subfamily due to decreased TREK-2 (KCNK10) mRNA within the mature SDH. Meanwhile, G-protein-coupled inward rectifying K(+) channels (K(ir)3.1 and K(ir)3.2) were expressed in the SDH at mature levels from birth. Overall, the results suggest that the transcription of ion channel genes occurs in a highly age-dependent manner within the SDH, raising the possibility that manipulating the expression or function of ion channels which are preferentially expressed within immature nociceptive networks could yield novel approaches to relieving pain in infants and children.
在幼年时期，啮齿动物脊髓背角浅层（SDH）中的神经元表现出明显的放电特性。虽然这可能反映了电压门控 Na(+)（Na(v)）和电压不依赖（即“泄漏”）K(+)通道的独特组合，这些通道强烈影响中枢神经系统中的神经元兴奋性，但令人惊讶的是，对于在发育中的脊髓疼痛回路中表达哪些基因编码 Na(v)和泄漏 K(+)通道知之甚少。因此，本研究的目的是使用定量实时聚合酶链反应在出生后第 3、10、21 天或成年期大鼠 SDH 中描述这些通道的转录表达。结果表明，Na(v)亚型在 mRNA 水平上以亚型特异性方式进行发育调控，Na(v)1.2 和 Na(v)1.3 从 P3 到成年期显著降低，而 Na(v)1.1 在这段时间内上调。数据还表明，双孔域（K(2P)）K(+)通道的 mRNA 表达存在选择性、年龄依赖性变化，因为 TWIK 相关酸敏感 K(+)通道 TASK-1（KCNK3）和 TASK-3（KCNK9）在出生后发育过程中下调，而在研究的串联孔域弱内向整流 K(+)通道（TWIK）亚型中没有任何变化（KCNK1 和 KCNK6）。此外，由于成熟 SDH 中 TREK-2（KCNK10）mRNA 的减少，TREK 亚家族发生了发育性转变。同时，G 蛋白偶联内向整流 K(+)通道（K(ir)3.1 和 K(ir)3.2）在出生时以成熟水平在 SDH 中表达。总体而言，结果表明，离子通道基因的转录在 SDH 中以高度年龄依赖性的方式发生，这增加了这样一种可能性，即操纵在不成熟伤害感受网络中优先表达的离子通道的表达或功能可能为缓解婴儿和儿童的疼痛提供新方法。
