Stone Audrey J, Copp Steven W, Kaufman Marc P
Heart and Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania.
Heart and Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania
Am J Physiol Regul Integr Comp Physiol. 2015 Nov 15;309(10):R1301-8. doi: 10.1152/ajpregu.00246.2015. Epub 2015 Aug 26.
Voltage-gated sodium channels (NaV) 1.7 are highly expressed on the axons of somatic afferent neurons and are thought to play an important role in the signaling of inflammatory pain. NaV 1.7 channels are classified as tetrodotoxin (TTX)-sensitive, meaning that they are blocked by TTX concentrations of less than 300 nM. These findings prompted us to determine in decerebrated, unanesthetized rats, the role played by NaV 1.7 channels in the transmission of muscle afferent input evoking the exercise pressor reflex. We first showed that the exercise pressor reflex, which was evoked by static contraction of the triceps surae muscles, was reversibly attenuated by application of 50 nM TTX, but not 5 nM TTX, to the L4-L5 dorsal roots (control: 21 ± 1 mmHg, TTX: 8 ± 2 mmHg, recovery: 21 ± 3 mmHg; n = 6; P < 0.01). We next found that the peak pressor responses to contraction were significantly attenuated by dorsal root application of 100 nM Ssm6a, a compound that is a selective NaV 1.7 channel inhibitor. Removal of Ssm6a restored the reflex to its control level (control: 19 ± 3 mmHg, Ssm6a: 10 ± 1 mmHg, recovery: 19 ± 4 mmHg; n = 6; P < 0.05). Compound action potentials recorded from the L4 and L5 dorsal roots and evoked by single-pulse stimulation of the sciatic nerve showed that both TTX and Ssm6a attenuated input from group III, as well as group IV afferents. We conclude that NaV 1.7 channels play a role in the thin-fiber muscle afferent pathway evoking the exercise pressor reflex.
电压门控钠通道（NaV）1.7在躯体传入神经元的轴突上高度表达，被认为在炎性疼痛信号传导中起重要作用。NaV 1.7通道被归类为对河豚毒素（TTX）敏感，这意味着它们会被浓度低于300 nM的TTX阻断。这些发现促使我们在去大脑、未麻醉的大鼠中确定NaV 1.7通道在引发运动升压反射的肌肉传入输入传递中所起的作用。我们首先表明，由腓肠肌静态收缩引发的运动升压反射，通过向L4-L5背根施加50 nM TTX可使其可逆性减弱，但施加5 nM TTX则无此效果（对照组：21±1 mmHg，TTX组：8±2 mmHg，恢复组：21±3 mmHg；n = 6；P < 0.01）。接下来我们发现，通过背根施加100 nM Ssm6a（一种选择性NaV 1.7通道抑制剂）可使对收缩的峰值升压反应显著减弱。去除Ssm6a后，反射恢复到对照水平（对照组：19±3 mmHg，Ssm6a组：10±1 mmHg，恢复组：19±4 mmHg；n = 6；P < 0.05）。从L4和L5背根记录的、由坐骨神经单脉冲刺激引发的复合动作电位表明，TTX和Ssm6a均减弱了来自III组以及IV组传入纤维的输入。我们得出结论，NaV 1.7通道在引发运动升压反射的细纤维肌肉传入通路中起作用。
