Sharopov Bizhan R, Gulak Kseniya L, Philyppov Igor B, Sotkis Anna V, Shuba Yaroslav M
Department of Nerve & Muscle Physiology, Bogomoletz Institute of Physiology NASU, Bogomotetz Str., 4, Kyiv 01024, Ukraine; Department of Biology, Faculty of Natural Sciences, National University of «Kyiv-Mohyla Academy», Skovoroda Str., 2, Kyiv 04655, Ukraine.
Department of Nerve & Muscle Physiology, Bogomoletz Institute of Physiology NASU, Bogomotetz Str., 4, Kyiv 01024, Ukraine.
Life Sci. 2018 Jan 15;193:207-213. doi: 10.1016/j.lfs.2017.10.042. Epub 2017 Oct 31.
More than half of diabetic patients experience voiding disorder termed diabetic urinary bladder dysfunction (DBD). Here we have investigated how the alterations in transient receptor potential vanilloid 1 (TRPV1) ion channel expressed in bladder-innervating afferents may contribute to DBD pathogenesis.
The rat model of streptozotocin (STZ)-induced diabetes was used. The functional profile of TRPV1 in retrogradely labeled afferent, bladder-innervating dorsal root ganglia (DRG) neurons was examined using patch clamp. The level of TRPV1 transcripts in DRG was assessed with qRT-PCR. TRPV1-dependent component of detrusor smooth muscle (DSM) contractions was studied with muscle strip tensiometry.
TRPV1-mediated current (I) was increased in diabetic animals vs. controls by 42%. The expression of Trpv1 gene was found to be 63% higher in STZ-treated rats compared to controls, consistent with the respective electrophysiological data. Surprisingly, capsaicin-induced contractions of DSM were found to be 3-to-10-fold weaker in diabetic group depending on concentration of the agonist (100nM to 10μM).
Our findings suggest the dual role of TRPV1 in DBD. On the one hand, the increase of its functional expression may enhance micturition reflex arc functioning. On the other hand, at the local level, the decrease of TRPV1-dependent contractions may contribute to organ decompensation.
超过半数的糖尿病患者会出现一种排尿障碍，称为糖尿病膀胱功能障碍（DBD）。在此，我们研究了膀胱传入神经中表达的瞬时受体电位香草酸受体1（TRPV1）离子通道的改变如何导致DBD的发病机制。
使用链脲佐菌素（STZ）诱导的糖尿病大鼠模型。采用膜片钳技术检测逆行标记的传入性膀胱支配背根神经节（DRG）神经元中TRPV1的功能特性。用qRT-PCR评估DRG中TRPV1转录本的水平。用肌肉条张力测定法研究逼尿肌平滑肌（DSM）收缩中TRPV1依赖的成分。
与对照组相比，糖尿病动物中TRPV1介导的电流（I）增加了42%。发现STZ处理的大鼠中Trpv1基因的表达比对照组高63%，这与各自的电生理数据一致。令人惊讶的是，根据激动剂浓度（100 nM至10 μM），糖尿病组中辣椒素诱导的DSM收缩减弱了3至10倍。
我们的研究结果表明TRPV1在DBD中具有双重作用。一方面，其功能表达的增加可能增强排尿反射弧的功能。另一方面，在局部水平，TRPV1依赖的收缩减弱可能导致器官失代偿。
