Basal lamina: A novel pH regulator at the neuromuscular junction.

Basal lamina: A novel pH regulator at the neuromuscular junction.
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DOI:
10.1177/00368504231225066
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发表时间:
2024-01
期刊:
影响因子:
2.1
通讯作者:
--
中科院分区:
综合性期刊4区
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--
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在突触活动期间,由于囊泡释放和 Ca2+ 从细胞区室中挤出,裂隙内的质子浓度可能会发生变化。突触间隙内的这些变化可以通过离子通道功能的质子依赖性调节来影响神经活动。突触之间的 pH 瞬变幅度和方向不同,需要测量不同的突触类型,以全面了解该机制及其对生理学的影响。最近发表的《小鼠神经肌肉接头处的突触后钙挤出使突触间隙碱化》以小鼠神经肌肉接头 (NMJ) 为重点,测量了胆碱能突触处的突触间隙 pH 值,发现了双相 pH 瞬变。研究表明,在测量肌肉膜的 pH 值时,质子浓度的变化是由突触后信号引起的,尽管人们预计会有突触前的影响。这一结果表明 NMJ 内的扩散屏障将突触前区室和突触后区室的 pH 瞬变隔离开来。产生影响质子的唐南平衡,有证据表明基底层可能是 NMJ pH 值的关键调节剂。探索突触 pH 值、质子调节因子以及突触前膜和突触后膜的下游 pH 瞬态效应可能会给多种疾病带来新的认识。
Proton concentration can change within the cleft during synaptic activity due to vesicular release and Ca2+ extrusion from cellular compartments. These changes within the synaptic cleft can impact neural activity by proton-dependent modulation of ion channel function. The pH transient differs in magnitude and direction between synapses, requiring different synapse types to be measured to generate a complete understanding of this mechanism and its impacts on physiology. With a focus on the mouse neuromuscular junction (NMJ), the recently published “Postsynaptic Calcium Extrusion at the Mouse Neuromuscular Junction Alkalinizes the Synaptic Cleft” measured synaptic cleft pH at a cholinergic synapse and found a biphasic pH transient. The study demonstrated that the changes in proton concentration found were due to postsynaptic signaling when measuring pH at the muscle membrane, despite the expectation of a presynaptic contribution. This result suggests a diffusional barrier within the NMJ isolates pH transients to presynaptic versus postsynaptic compartments. Generating a Donnan equilibrium that impacts protons, evidence suggests the basal lamina may be a key regulator of pH at the NMJ. Exploring synaptic pH, proton regulating factors, and downstream pH transient effects at presynaptic versus postsynaptic membranes may lead to new insight for a variety of diseases.
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