Zagorodnyuk Vladimir P, Gibbins Ian L, Costa Marcello, Brookes Simon J H, Gregory Sarah J
Department of Human Physiology, Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia.
J Physiol. 2007 Nov 15;585(Pt 1):147-63. doi: 10.1113/jphysiol.2007.140244. Epub 2007 Oct 4.
Sensory neurons represent an attractive target for pharmacological treatment of various bladder disorders. However the properties of major classes of mechano-sensory neurons projecting to the bladder have not been systematically established. An in vitro bladder preparation was used to examine the effects of a range of mechanical stimuli (stretch, von Frey hair stroking and focal compression of receptive fields) and chemical stimuli (1 mm alpha,beta-methylene ATP, hypertonic solutions (500 mm NaCl) and 3 microm capsaicin) during electrophysiological recordings from guinea pig bladder afferents. Four functionally distinct populations of bladder sensory neurons were distinguished by these stimuli. The first class, muscle mechanoreceptors, were activated by stretch but not by mucosal stroking with light (0.05-0.1 mN) von Frey hairs or by hypertonic saline, alpha,beta-methylene ATP or capsaicin. Removal of the urothelium did not affect their stretch-induced firing. The second class, muscle-mucosal mechanoreceptors, were activated by both stretch and mucosal stroking with light von Frey hairs or by hypertonic saline and by alpha,beta-methylene ATP, but not by capsaicin. Removal of the urothelium reduced their stretch- and stroking-induced firing. The third class, mucosal high-responding mechanoreceptors, were stretch-insensitive but could be activated by mucosal stroking with light von Frey hairs or by hypertonic saline, alpha,beta-methylene ATP and capsaicin. Stroking-induced firing was significantly reduced by removal of the urothelium. The fourth class, mucosal low-responding mechanoreceptors, were stretch insensitive but could be weakly activated by mucosal stroking with light von Frey hairs but not by hypertonic saline, alpha,beta-methylene ATP or capsaicin. Removal of the urothelium reduced mucosal stroking-induced firing. All four populations of afferents conducted in the C-fibre range and showed class-dependent differences in spike amplitude and duration. At least four functional classes of bladder mechanoreceptors can be readily distinguished by different mechanisms of activation and are likely to transmit different types of information to the central nervous system.
感觉神经元是各种膀胱疾病药物治疗的一个有吸引力的靶点。然而,投射到膀胱的主要机械感觉神经元类别的特性尚未得到系统确立。使用体外膀胱制备物,在豚鼠膀胱传入神经的电生理记录过程中,检测一系列机械刺激(拉伸、用von Frey毛轻触和感受野的局部压迫)和化学刺激(1 mM α,β-亚甲基ATP、高渗溶液(500 mM NaCl)和3 μM辣椒素)的作用。通过这些刺激区分出了四种功能不同的膀胱感觉神经元群体。第一类,肌肉机械感受器,由拉伸激活,但不受用轻(0.05 - 0.1 mN)von Frey毛进行的黏膜轻触、高渗盐水、α,β-亚甲基ATP或辣椒素激活。去除尿路上皮不影响其拉伸诱导的放电。第二类,肌肉 - 黏膜机械感受器,由拉伸和用轻von Frey毛进行的黏膜轻触、高渗盐水或α,β-亚甲基ATP激活,但不受辣椒素激活。去除尿路上皮会降低其拉伸和轻触诱导的放电。第三类,黏膜高反应性机械感受器,对拉伸不敏感,但可由用轻von Frey毛进行的黏膜轻触、高渗盐水、α,β-亚甲基ATP和辣椒素激活。去除尿路上皮会显著降低轻触诱导的放电。第四类,黏膜低反应性机械感受器,对拉伸不敏感,但可由用轻von Frey毛进行的黏膜轻触微弱激活,但不受高渗盐水、α,β-亚甲基ATP或辣椒素激活。去除尿路上皮会降低黏膜轻触诱导的放电。所有四类传入神经都在C纤维范围内传导,并且在动作电位幅度和持续时间上表现出类别依赖性差异。至少四种功能类别的膀胱机械感受器可以通过不同的激活机制轻易区分,并且可能向中枢神经系统传递不同类型的信息。