Bichler Edyta K, Carrasco Dario I, Rich Mark M, Cope Timothy C, Pinter Martin J
Department of Physiology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
J Physiol. 2007 Nov 15;585(Pt 1):47-56. doi: 10.1113/jphysiol.2007.135541. Epub 2007 Sep 20.
Available evidence supports the idea that muscle fibres provide retrograde signals that enable the expression of adult motoneuron electrical properties but the mechanisms remain unknown. We showed recently that when acetylcholine receptors are blocked at motor endplates, the electrical properties of rat motoneurons change in a way that resembles changes observed after axotomy. This observation suggests that receptor blockade and axotomy interrupt the same signalling mechanisms but leaves open the possibility that the loss of muscle fibre activity underlies the observed effects. To address this issue, we examined the electrical properties of axotomized motoneurons following reinnervation. Ordinarily, these properties return to normal following reinnervation and re-activation of muscle, but in this study muscle fibre activity and evoked acetylcholine release were prevented during reinnervation by blocking axonal conduction. Under these conditions, the properties of motoneurons that successfully reinnervated muscle fibres recovered to normal despite the absence of muscle fibre activity and evoked release. We conclude that the expression of motoneuron electrical properties is not regulated by muscle fibre activity but rather by a retrograde signalling system coupled to activation of endplate acetylcholine receptors. Our results indicate that spontaneous release of acetylcholine from regenerated motor terminals is sufficient to operate the system.
现有证据支持这样一种观点,即肌纤维提供逆行信号,使成年运动神经元的电特性得以表达,但具体机制仍不清楚。我们最近发现,当运动终板处的乙酰胆碱受体被阻断时,大鼠运动神经元的电特性会以一种类似于轴突切断后观察到的变化方式发生改变。这一观察结果表明,受体阻断和轴突切断中断了相同的信号传导机制,但也留下了一种可能性,即肌纤维活动的丧失是观察到的效应的基础。为了解决这个问题,我们研究了轴突切断的运动神经元在重新支配后的电特性。通常情况下,这些特性在肌肉重新支配和重新激活后会恢复正常,但在本研究中,在重新支配期间通过阻断轴突传导来防止肌纤维活动和诱发的乙酰胆碱释放。在这些条件下,成功重新支配肌纤维的运动神经元的特性尽管没有肌纤维活动和诱发释放,但仍恢复到正常。我们得出结论,运动神经元电特性的表达不是由肌纤维活动调节的,而是由与终板乙酰胆碱受体激活相关的逆行信号系统调节的。我们的结果表明,再生运动终末乙酰胆碱的自发释放足以使该系统发挥作用。