Carew Josephine A, Cristofaro Vivian, Dasari Suhas P, Carey Sean, Goyal Raj K, Sullivan Maryrose P
Urology Research, VA Boston Healthcare System, Boston, MA, United States.
Harvard Medical School, Boston, MA, United States.
Front Physiol. 2022 Jul 1;13:890102. doi: 10.3389/fphys.2022.890102. eCollection 2022.
Dysregulation of neurotransmission is a feature of several prevalent lower urinary tract conditions, but the mechanisms regulating neurotransmitter release in the bladder are not completely understood. The unconventional motor protein, Myosin 5a, transports neurotransmitter-containing synaptic vesicles along actin fibers towards the varicosity membrane, tethering them at the active zone prior to reception of a nerve impulse. Our previous studies indicated that Myosin 5a is expressed and functionally relevant in the peripheral nerves of visceral organs such as the stomach and the . However, its potential role in bladder neurotransmission has not previously been investigated. The expression of was examined by quantitative PCR and restriction analyses in bladders from DBA (dilute-brown-nonagouti) mice which express a Myosin 5a splicing defect and in control mice expressing the wild-type allele. Functional differences in contractile responses to intramural nerve stimulation were examined by isometric tension analysis. Data demonstrated Myosin 5a localized in cholinergic nerve fibers in the bladder and identified several Myosin 5a splice variants in the detrusor. Full-length Myosin 5a transcripts were less abundant and the expression of splice variants was altered in DBA bladders compared to control bladders. Moreover, attenuation of neurally-mediated contractile responses in DBA bladders compared to control bladders indicates that Myosin 5a facilitates excitatory neurotransmission in the bladder. Therefore, the array of Myosin 5a splice variants expressed, and the abundance of each, may be critical parameters for efficient synaptic vesicle transport and neurotransmission in the urinary bladder.
神经传递失调是几种常见下尿路疾病的一个特征，但调节膀胱中神经递质释放的机制尚未完全明确。非常规运动蛋白肌球蛋白5a沿着肌动蛋白纤维将含神经递质的突触小泡向曲张膜运输，并在接收神经冲动之前将它们系于活性区。我们之前的研究表明，肌球蛋白5a在内脏器官如胃和[此处原文缺失器官名称]的外周神经中表达且具有功能相关性。然而，其在膀胱神经传递中的潜在作用此前尚未被研究。通过定量PCR和限制性分析检测了表达肌球蛋白5a剪接缺陷的DBA（稀释棕色非阿高蒂）小鼠膀胱以及表达野生型[此处原文缺失相关基因名称]等位基因的对照小鼠膀胱中[此处原文缺失相关基因名称]的表达。通过等长张力分析检测了对壁内神经刺激的收缩反应的功能差异。数据表明肌球蛋白5a定位于膀胱中的胆碱能神经纤维，并在逼尿肌中鉴定出几种肌球蛋白5a剪接变体。与对照膀胱相比，DBA膀胱中全长肌球蛋白5a转录本丰度较低且剪接变体的表达发生了改变。此外，与对照膀胱相比，DBA膀胱中神经介导的收缩反应减弱表明肌球蛋白5a促进膀胱中的兴奋性神经传递。因此，所表达的肌球蛋白5a剪接变体阵列及其各自的丰度可能是膀胱中高效突触小泡运输和神经传递的关键参数。
