Woon Eric, Santeli Jorge Villalobos, Liu Jia, Chen Longtu, Kuchel George, Feng Bin
Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, USA.
UConn Center on Aging, UConn Health, Farmington, Connecticut, USA.
Low Urin Tract Symptoms. 2025 Sep;17(5):e70025. doi: 10.1111/luts.70025.
This study aimed to investigate the potential role of cesium chloride (CsCl), ivabradine (IVA), and isoproterenol (ISO) on the sensory transmission of bladder afferents to graded urinary bladder distension (UBD). We specifically selected these drugs to target the hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels to determine their role in afferent encoding.
The bladders of C57BL/6 female mice were harvested with attached pelvic nerves in continuity, and the stimulus-response function (SRF) of bladder afferents to stepped bladder distension (20, 40, 60, 80 cmHO) was recorded by single-fiber recordings. Their changes in SRF to bath application of CsCl, IVA, and ISO were then evaluated. The presence of HCN on bladder afferent endings was assessed through immunohistological staining on bladder sections from mice with genetically labeled bladder afferents.
IVA and ISO did not significantly reduce afferent responses to UBD, whereas CsCl increased afferent responses. Bladder afferents in the pelvic nerve pathway were categorized into low-firing (LF, < 10 Hz) and high-firing (HF, > 10 Hz) groups. SRF in both the LF and HF groups showed similar trends with no significant changes in response to IVA and ISO. CsCl increased SRF only in the HF group but not in the LF group. Immunohistological staining revealed that HCN1 does not extensively co-localize with afferent endings, showing only sporadic presence.
Our targeted pharmacological studies with single-fiber recordings and immunohistological staining collectively suggest that HCN channels do not play a significant role in bladder afferent sensory transmission.
本研究旨在探讨氯化铯（CsCl）、伊伐布雷定（IVA）和异丙肾上腺素（ISO）对膀胱传入神经向分级膀胱扩张（UBD）的感觉传递的潜在作用。我们特意选择这些药物作用于超极化激活的环核苷酸门控（HCN）阳离子通道，以确定它们在传入编码中的作用。
连续摘取C57BL/6雌性小鼠的膀胱及其相连的盆神经，通过单纤维记录法记录膀胱传入神经对阶梯式膀胱扩张（20、40、60、80 cmH₂O）的刺激-反应函数（SRF）。然后评估它们对浴加CsCl、IVA和ISO时SRF的变化。通过对具有基因标记膀胱传入神经的小鼠膀胱切片进行免疫组织化学染色，评估膀胱传入神经末梢上HCN的存在情况。
IVA和ISO并未显著降低对UBD的传入反应，而CsCl增加了传入反应。盆神经通路中的膀胱传入神经分为低发放（LF，<10 Hz）和高发放（HF，>10 Hz）两组。LF组和HF组的SRF显示出相似的趋势，对IVA和ISO的反应无显著变化。CsCl仅增加了HF组的SRF，而未增加LF组的SRF。免疫组织化学染色显示，HCN1与传入神经末梢没有广泛共定位，仅偶尔存在。
我们通过单纤维记录和免疫组织化学染色进行的靶向药理学研究共同表明，HCN通道在膀胱传入感觉传递中不发挥重要作用。
