Khaziev Arthur N, Tsentsevitsky Andrei N, Fedorov Nikita S, Kuznetsova Eva A, Malomouzh Artem I, Petukhova Elena O, Salnikov Vadim V, Kovyazina Irina V, Petrov Alexey M
Kazan Institute of Biochemistry and Biophysics, Federal Research Center "Kazan Scientific Center of RAS", 2/31 Lobachevsky Street, Box 261, Kazan, 420111, Russia.
Kazan National Research Technical University, 10, K. Marx Street, Kazan, 420111, Russia.
Biometals. 2025 Aug 27. doi: 10.1007/s10534-025-00740-3.
Zinc (Zn) is the second most abundant trace element after iron, with most of it is stored in skeletal muscles. Although a large part of Zn is tightly bound to metalloproteins, the small portion of free Zn can participate in nerve signaling. Here we examined the effects of Zn at nanomolar concentrations on neuromuscular transmission in the diaphragm, the main respiratory muscle. Zn reduced spontaneous neurotransmitter release at both lowered and physiological external Ca levels. Additionally, Zn effectively decreased the probability of neurotransmitter release upon single nerve stimulation under lowered external Ca, and inhibited Ca-independent sucrose-induced exocytosis. At physiological external Ca concentration, Zn decreased neurotransmitter release during low-frequency stimulation. The reduction became increased during short trains of moderate-to-high frequency stimuli. Furthermore, Zn diminished both neurotransmitter release and the participation of dye-labeled synaptic vesicles in exocytosis during prolonged nerve firing at moderate frequency. Zn aggravated muscle fatigue and impaired contraction recovery upon nerve stimulation. This was linked to a reduction in peak inspiratory flow in mice, an indicator of diaphragm function, after injection of low-dose Zn. Our data suggest that at nanomolar concentrations, Zn is a negative modulator of neuromuscular function.
锌（Zn）是仅次于铁的第二丰富的微量元素，其中大部分储存在骨骼肌中。尽管大部分锌与金属蛋白紧密结合，但少量的游离锌可参与神经信号传导。在这里，我们研究了纳摩尔浓度的锌对主要呼吸肌膈肌神经肌肉传递的影响。在降低的和生理水平的细胞外钙浓度下，锌均减少了自发性神经递质释放。此外，在降低的细胞外钙浓度下，锌有效降低了单次神经刺激时神经递质释放的概率，并抑制了与钙无关的蔗糖诱导的胞吐作用。在生理细胞外钙浓度下，锌在低频刺激时减少神经递质释放。在中高频刺激的短串刺激期间，这种减少变得更加明显。此外，在中等频率的长时间神经放电期间，锌减少了神经递质释放以及染料标记的突触小泡参与胞吐作用。锌加剧了肌肉疲劳，并损害了神经刺激后的收缩恢复。这与注射低剂量锌后小鼠的峰值吸气流量降低有关，峰值吸气流量是膈肌功能的一个指标。我们的数据表明，在纳摩尔浓度下，锌是神经肌肉功能的负调节剂。
