HCN as a Mediator of Urinary Homeostasis: Age-Associated Changes in Expression and Function in Adrenergic Detrusor Relaxation
HCN as a Mediator of Urinary Homeostasis: Age-Associated Changes in Expression and Function in Adrenergic Detrusor Relaxation
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DOI：
10.1093/gerona/gly137
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发表时间：
2019-03-01
影响因子：
5.1
通讯作者：
Smith, Phillip P.
中科院分区：
文献类型：
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作者：
Al-Naggar, Iman M.;Hardy, Cara C.;Smith, Phillip P.
超极化激活的环核苷酸门控（HCN）通道是充盈过程中神经内分泌对逼尿肌张力影响的候选介质。在其他组织中，随着年龄的增长，HCN的丧失与节律性和功能的下降有关。我们假设HCN在肾上腺素能性膀胱松弛中具有年龄敏感性表达谱和功能作用。采用qRT-PCR、RNAScope和Western blots检测幼年（2-6月龄）和老年（18-24月龄）C57BL/6雌性小鼠膀胱中的HCN。采用幼年野生型（YWT）、老年野生型（OWT）和幼年HCN1敲除（YKO）雌性小鼠膀胱条进行等长张力实验，以测试HCN在β -肾上腺素能刺激中的作用。Hcn1是小鼠膀胱壁中主要的HCN亚型RNA，随着年龄的增长而减少。Hcn RNA在小鼠膀胱壁上的位置是同型特异性的，HCN1局限于逼尿肌层。在存在HCN功能的情况下，被动张力的YWT膀胱条被异丙肾上腺素松弛，而OWT条仅在存在HCN阻断的情况下松弛。HCN在小鼠膀胱条带肾上腺素能逼尿肌松弛中具有年龄特异性表达和功能。
The Hyperpolarization activated, cyclic nucleotide gated (HCN) channel is a candidate mediator of neuroendocrine influence over detrusor tonus during filling. In other tissues, HCN loss with aging is linked to declines in rhythmicity and function. We hypothesized that HCN has an age-sensitive expression profile and functional role in adrenergic bladder relaxation. HCN was examined in bladders from young (2-6 months) and old (18-24 months) C57BL/6 female mice, using qRT-PCR, RNAScope, and Western blots. Isometric tension studies were conducted using bladder strips from young wild-type (YWT), old wild-type (OWT), and young HCN1 knock-out (YKO) female mice to test the role HCN in effects of beta-adrenergic stimulation. Hcn1 is the dominant HCN isoform RNA in the mouse bladder wall, and is diminished with age. Location of Hcn RNA within the mouse bladder wall is isoform-specific, with HCN1 limited to the detrusor layer. Passively-tensioned YWT bladder strips are relaxed by isoproterenol in the presence of HCN function, where OWT strips are relaxed only in the presence of HCN blockade. HCN has an age-specific expression and function in adrenergic detrusor relaxation in mouse bladder strips.