University of Tennessee Health Science Center, Department of Anatomy and Neurobiology, 855 Monroe Avenue, TN, USA.
Neuroscience. 2012 Oct 11;222:205-14. doi: 10.1016/j.neuroscience.2012.07.012. Epub 2012 Jul 16.
The distribution of low-threshold tetrodotoxin-resistant (TTX-r) Na(+) current and its co-expression with high-threshold TTX-r Na(+) current were studied in randomly selected acutely dissociated rat trigeminal ganglion (non-identified TG cells) and TG cells serving the temporomandibular joint (TMJ-TG cells). Conditions previously shown to enhance Na(V)1.9 channel-mediated currents (holding potential (HP) -80 mV, 130-mM fluoride internally) were employed to amplify the low-threshold Na(+) current. Under these conditions, detectable low-threshold Na(+) current was exhibited by 16 out of 21 non-identified TG cells (average, 1810 ± 358 pA), and by nine of 14 TMJ-TG cells (average, 959 ± 525 pA). The low-threshold Na(+) current began to activate around -55 mV and was inactivated by holding TG cells at -60 mV and delivering 40-ms test potentials (TPs) to 0 mV. The inactivation was long lasting, recovering only 8 ± 3% over a 5-min period after the HP was returned to -80 mV. Following low-threshold Na(+) current inactivation, high-threshold TTX-r Na(+) current, evoked from HP -60 mV, was observed. High-threshold Na(+) current amplitude averaged 16,592 ± 3913 pA for TPs to 0 mV, was first detectable at an average TP of -34 ± 1.3 mV, and was ½ activated at -7.1 ± 2.3 mV. In TG cells expressing prominent low-threshold Na(+) currents, changing the external solution to one containing 0 mM Na(+) reduced the amount of current required to hold the cells at -80 mV through -50 mV, the peak effect being observed at HP -60 mV. TG cells recorded from with a more physiological pipette solution containing chloride instead of fluoride exhibited small low-threshold Na(+) currents, which were greatly increased upon superfusion of the TG cells with the adenylyl cyclase (AC) activator forskolin. These data suggest two hypotheses: (1) low- and high-threshold Na(V)1.9 and Na(V)1.8 channels, respectively, are frequently co-expressed in TG neurons serving the TMJ and other structures, and (2), Na(V)1.9 channel-mediated currents are small under physiological conditions, but may be enhanced by inflammatory mediators that increase AC activity, and may mediate an inward leak that depolarizes TG neurons, increasing their excitability.
研究了随机分离的大鼠三叉神经节（未鉴定的 TG 细胞）和服务于颞下颌关节的 TG 细胞（TMJ-TG 细胞）中低阈值河豚毒素抗性（TTX-r）Na(+)电流的分布及其与高阈值 TTX-r Na(+)电流的共表达。先前已证明可增强 Na(V)1.9 通道介导的电流的条件（保持电位（HP）-80 mV，内部 130 mM 氟化物）被用来放大低阈值 Na(+)电流。在这些条件下，21 个未鉴定的 TG 细胞中有 16 个（平均 1810 ± 358 pA）和 14 个 TMJ-TG 细胞中有 9 个（平均 959 ± 525 pA）可检测到低阈值 Na(+)电流。低阈值 Na(+)电流在约-55 mV 时开始激活，并在将 TG 细胞保持在-60 mV 并将 40-ms 测试电位（TP）输送至 0 mV 时失活。失活持续时间长，在 HP 恢复到-80 mV 后 5 分钟内仅恢复 8 ± 3%。在低阈值 Na(+)电流失活后，从 HP -60 mV 激发观察到高阈值 TTX-r Na(+)电流。高阈值 Na(+)电流幅度平均为 16,592 ± 3913 pA，用于 TP 至 0 mV，在平均 TP -34 ± 1.3 mV 时首次可检测到，并且在-7.1 ± 2.3 mV 时被激活 1/2。在表达明显低阈值 Na(+)电流的 TG 细胞中，将外部溶液更改为不含 Na(+)的溶液可减少将细胞保持在-80 mV 通过-50 mV 所需的电流，最大效果在 HP -60 mV 时观察到。从含有氯离子而不是氟化物的更生理的管溶液中记录的 TG 细胞显示出小的低阈值 Na(+)电流，当用激活腺苷酸环化酶（AC）的 forskolin超流 TG 细胞时，这些电流大大增加。这些数据表明两个假设：（1）低阈值和高阈值 Na(V)1.9 和 Na(V)1.8 通道分别在服务于 TMJ 和其他结构的 TG 神经元中经常共表达，（2），Na(V)1.9 通道介导的电流在生理条件下很小，但可能被增加 AC 活性的炎症介质增强，并且可能介导使 TG 神经元去极化从而增加其兴奋性的内向漏电流。
