Matsuyoshi Hiroko, Masuda Noriyuki, Chancellor Michael B, Erickson Vickie L, Hirao Yoshihiko, de Groat William C, Wanaka Akio, Yoshimura Naoki
Department of Urology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Brain Res. 2006 Nov 13;1119(1):115-23. doi: 10.1016/j.brainres.2006.08.052. Epub 2006 Sep 18.
Afferent pathways innervating the urinary bladder consist of myelinated Adelta- and unmyelinated C-fibers, the neuronal cell bodies of which correspond to medium and small-sized cell populations of dorsal root ganglion (DRG) neurons, respectively. Since hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel currents have been identified in various peripheral sensory neurons, we examined the expression of isoforms of HCN channels in the L6-S1 spinal cord and bladder afferent neurons from L6-S1 DRG in rats. Among HCN-1, HCN-2 and HCN-4 channel subtypes, positive staining with HCN-2 antibodies was found in the superficial dorsal horn of the spinal cord and small- and medium-sized unidentified DRG neurons. In dye-labeled bladder afferent neurons, HCN-2-positive cells were found in approximately 60% of neurons, and HCN-2 was expressed in both small- and medium-sized neurons with a higher ratio (expression ratio: 61% and 50% of neurons, respectively) compared with unidentified DRG neurons, in which the HCN expression ratio was 47% and 21% of small- and medium-sized cells, respectively. These results suggest that HCN-2 is the predominant subtype of HCN channels, which can control neuronal excitability, in small-sized C-fiber and medium-sized Adelta fiber DRG neurons including bladder afferent neurons, and might modulate activity of bladder afferent pathways controlling the micturition reflex.
支配膀胱的传入通路由有髓鞘的 Aδ 纤维和无髓鞘的 C 纤维组成，其神经元细胞体分别对应于背根神经节（DRG）神经元中的中小细胞群。由于在各种外周感觉神经元中已鉴定出超极化激活的环核苷酸门控阳离子（HCN）通道电流，我们研究了大鼠 L6 - S1 脊髓和 L6 - S1 DRG 膀胱传入神经元中 HCN 通道亚型的表达。在 HCN - 1、HCN - 2 和 HCN - 4 通道亚型中，在脊髓浅表背角和中小型未鉴定的 DRG 神经元中发现了 HCN - 2 抗体的阳性染色。在染料标记的膀胱传入神经元中，约 60%的神经元中发现了 HCN - 2 阳性细胞，并且与未鉴定的 DRG 神经元相比，HCN - 2 在中小型神经元中均有表达，比例更高（表达比例：分别为神经元的 61%和 50%），在未鉴定的 DRG 神经元中，HCN 在小细胞和中细胞中的表达比例分别为 47%和 21%。这些结果表明，HCN - 2 是 HCN 通道的主要亚型，可控制包括膀胱传入神经元在内的小尺寸 C 纤维和中尺寸 Aδ 纤维 DRG 神经元的神经元兴奋性，并可能调节控制排尿反射的膀胱传入通路的活动。
