Tadros Melissa A, Farrell Kristen E, Graham Brett A, Brichta Alan M, Callister Robert J
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine and Hunter Medical Research Institute, The University of Newcastle, Callaghan, Newcastle, NSW, 2308, Australia.
Mol Pain. 2015 Mar 28;11:17. doi: 10.1186/s12990-015-0014-5.
Superficial dorsal horn (SDH) neurons process nociceptive information and their excitability is partly determined by the properties of voltage-gated sodium channels. Recently, we showed the excitability and action potential properties of mouse SDH neurons change markedly during early postnatal development. Here we compare sodium currents generated in neonate (P0-5) and young adult (≥P21) SDH neurons.
Whole cell recordings were obtained from lumbar SDH neurons in transverse spinal cord slices (CsF internal, 32°C). Fast activating and inactivating TTX-sensitive inward currents were evoked by depolarization from a holding potential of -100 mV. Poorly clamped currents, based on a deflection in the IV relationship at potentials between -60 and -50 mV, were not accepted for analysis. Current density and decay time increased significantly between the first and third weeks of postnatal development, whereas time to peak was similar at both ages. This was accompanied by more subtle changes in activation range and steady state inactivation. Recovery from inactivation was slower and TTX-sensitivity was reduced in young adult neurons.
Our study suggests sodium channel expression changes markedly during early postnatal development in mouse SDH neurons. The methods employed in this study can now be applied to future investigations of spinal cord sodium channel plasticity in murine pain models.
脊髓背角浅层(SDH)神经元处理伤害性信息,其兴奋性部分由电压门控钠通道的特性决定。最近,我们发现小鼠SDH神经元的兴奋性和动作电位特性在出生后早期发育过程中发生显著变化。在此,我们比较新生(P0 - 5)和年轻成年(≥P21)SDH神经元产生的钠电流。
在横断脊髓切片(内部溶液为CsF,32°C)中从腰段SDH神经元获得全细胞记录。通过从 - 100 mV的钳制电位去极化诱发快速激活和失活的TTX敏感内向电流。基于 - 60至 - 50 mV电位之间IV关系的偏转而出现的钳制不佳电流不纳入分析。出生后发育的第一周和第三周之间,电流密度和衰减时间显著增加,而两个年龄段的峰值时间相似。这伴随着激活范围和稳态失活的更细微变化。年轻成年神经元的失活恢复较慢且TTX敏感性降低。
我们的研究表明,小鼠SDH神经元在出生后早期发育过程中钠通道表达发生显著变化。本研究中采用的方法现在可应用于未来对小鼠疼痛模型中脊髓钠通道可塑性的研究。