38 INCREASED EXCITABILITY OF BLADDER AFFERENT NEURONS IN RATS WITH SPINAL CORD INJURY: A ROLE OF A-TYPE VOLTAGE-GATED POTASSIUM CHANNELS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201238 INCREASED EXCITABILITY OF BLADDER AFFERENT NEURONS IN RATS WITH SPINAL CORD INJURY: A ROLE OF A-TYPE VOLTAGE-GATED POTASSIUM CHANNELS Ryosuke Takahashi, Takakazu Yunoki, Seiji Naito, and Naoki Yoshimura Ryosuke TakahashiRyosuke Takahashi Pittsburgh, PA More articles by this author , Takakazu YunokiTakakazu Yunoki Fukuoka, Japan More articles by this author , Seiji NaitoSeiji Naito Fukuoka, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.081AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although the etiology of overactive bladder (OAB) seems to be mutifactorial, afferent sensitization is considered to contribute to OAB symptoms such as urgency. Also, increased excitability of C-fiber afferent pathways has been proposed as an important pathophysiological basis of neurogenic detrusor overactivity (DO) in humans and animals with spinal cord injury (SCI). However, the functional mechanisms inducing hyperexcitability of C-fiber bladder afferent neurons (B-AN) after SCI are not fully elucidated We therefore examined changes in electrophysiological properties of B-AN obtained from SCI rats, especially focusing on voltage-gated potassium channels that can reduce cell excitability, using patch-clamp recording techniques. METHODS SCI was produced by transection of the spinal cord at the level of T9-T10 in female SD rats. After 4 weeks, L6-S1 dorsal root ganglia (DRG) were removed from spinal intact and SCI rats, and freshly dissociated DRG neurons were prepared with enzymatic methods. Whole cell patch-clamp recordings were performed on individual B-AN, which were labeled by retrograde axonal transport of a fluorescent dye, Fast Blue (FB), injected into the bladder wall 7 days earlier and identified with a fluorescent microscope. Since the majority of C-fiber B-AN are sensitive to capsaicin, FB-labeled cells that exhibited inward currents in response to capsaicin (500nM) application were selected for evaluation. RESULTS Capsaicin-sensitive B-AN from SCI rats exhibited lower thresholds for spike activation (−26.4±1.3mV) than those from control rats (−21.8±0.9mV) and did not exhibit membrane potential relaxation during membrane depolarization. The number of firing during a 800 msec depolarizing pulse was significantly increased after SCI (4.7±0.7 spikes) compared to control rats (1.3±0.1 spikes). The peak density of A-type potassium (KA) currents during membrane depolarizations to 0mV in capsaicin-sensitive B-AN of SCI rats was significantly smaller (38.1±4.6 pA/pF) than that from control rats (68.6±6.3 pA/pF), and the inactivation curve of the KA current was displaced to more hyperpolarized levels by ∼10mV after SCI, indicating a reduction in KA channel function. On the other hand, the sustained delayed-rectifier potassium current density was not altered after SCI. CONCLUSIONS These results suggest that reduced KA channel activity is involved in hyperexcitability of capsaicin-sensitive C-fiber B-AN after SCI. Thus, the KA channel could be a potential target for treating OAB due to neurogenic DO. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e16 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryosuke Takahashi Pittsburgh, PA More articles by this author Takakazu Yunoki Fukuoka, Japan More articles by this author Seiji Naito Fukuoka, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...