经颅磁声电刺激对老年小鼠电压门控钠钾离子通道的影响

Effects of transcranial magneto-acousto-electrical stimulation on voltage-gated sodium and potassium channels in aged mice

背景:经颅磁声电刺激是一种新型无创的神经调控技术,利用超声波与静磁场耦合作用产生的感应电场调节神经系统的放电活动,但其作用机制目前尚不清楚。目的:探讨经颅磁声电刺激调节老年小鼠神经兴奋性变化的内在介导机制。方法:取20只老年(15月龄)昆明小鼠,采用随机数字表法分为老年对照组(接受伪刺激)、磁场组(仅接受0.3 T的静磁场刺激)、超声组(仅接受2.6 W/cm^(2)的超声刺激)和磁声组(接受0.3 T静磁场、2.6 W/cm^(2)超声的耦合刺激),每组5只,刺激2 min/d,连续刺激14 d;另将5只青年(2月龄)昆明小鼠作为青年组(接受伪刺激)。刺激结束后,采用膜片钳技术分别记录小鼠脑切片中细胞激活、失活和复活过程中相关通道的离子电流。结果与结论:①与老年对照组比较,磁声组小鼠电压门控钠通道电流峰值升高(P<0.05),通道电流的激活曲线向左移动,失活曲线向右移动,恢复活性时间缩短(P<0.05),与青年组仍有差距(P<0.05);磁声组小鼠电压门控钾通道电流峰值降低(P<0.05),瞬时外向钾电流和延迟整流钾电流的激活曲线均向右移动,瞬时外向钾电流的失活曲线向左移动,瞬时外向钾电流的恢复活性时间延长(P<0.05),与青年组仍有差距(P<0.05);②结果表明,经颅磁声电刺激可以通过相关离子通道动力学特性的改变,产生激活钠离子电流并抑制钾离子电流的效果,进而提高老年小鼠的神经兴奋性,但尚不能达到青年小鼠的水平,这种神经调控技术有望为延缓衰老提供潜在的可能性。

BACKGROUND:Transcranial magneto-acousto-electrical stimulation(TMAES)is a new non-invasive neuromodulation technique,which uses the induced field generated by the coupling of ultrasound and static magnetic fields to regulate the firing activity of the nervous system,but the mechanism of its neuromodulatory effect is not yet clear.OBJECTIVE:To explore the intrinsic mediating mechanism of TMAES regulating the changes of neural excitability in aged mice.METHODS:Twenty aged mice were equally and randomly divided into aged control group(receiving pseudo-stimulation),magnetic field group(receiving 0.3 T static magnetic field stimulation),ultrasound group(receiving 2.6 W/cm^(2) ultrasound stimulation),and magneto-acoustical group(receiving 0.3 T and 2.6 W/cm^(2) coupling stimulation),with five mice in each group.Simulation in each group was done 2 minutes per day for 14 continuous days.Another five young mice(2 months of age)served as the young group(receiving pseudo-stimulation).Then,patch-clamp technique was used to record the ionic currents of relevant channels during cell activation,inactivation,and reactivation in brain slices of mice.RESULTS AND CONCLUSION:Compared with the aged control group,TMAES significantly increased the current peak value of sodium channels(P<0.05),shifted the activation curve of voltage-gated sodium channel currents to the left,shifted the inactivation curve to the right,and shortened the reactivation time(P<0.05).However,there was a significant difference between magneto-acoustical and young groups(P<0.05).Compared with the aged control group,TMAES suppressed the current peaks of potassium channels,shifted the activation curves of both transient outward potassium currents and delayed rectifier potassium currents to the right,shifted the inactivation curves of transient outward potassium currents to the left,and extended the reactivation time of transient outward potassium currents.However,there was still a significant difference between magneto-acoustical and young groups(P<0.05).All these findings indicate that TMAES can activate sodium currents and inhibit potassium currents through altering the dynamic characteristics of relevant ion channels,thereby improving the neural excitability of aged mice,but not up to the level of young mice.This neuromodulation technique is expected to provide potential possibilities for delaying aging.