1707 INCREASED EXCITABILITY OF BLADDER AFFERENT NEURONS ASSOCIATED WITH REDUCED EXPRESSION OF KV1.4 α-SUBUNIT IN RATS WITH SPINAL CORD INJURY

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction1 Apr 20131707 INCREASED EXCITABILITY OF BLADDER AFFERENT NEURONS ASSOCIATED WITH REDUCED EXPRESSION OF KV1.4 α-SUBUNIT IN RATS WITH SPINAL CORD INJURY Ryosuke Takahashi, Takakazu Yunoki, Seiji Naito, and Naoki Yoshimura Ryosuke TakahashiRyosuke Takahashi Fukuoka, Japan 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.2013.02.2953AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Hyperexcitability of C-fiber bladder afferent pathways has been proposed as an important pathophysiological basis of neurogenic detrusor overactivity with spinal cord injury (SCI). However, the molecular 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 and the expression levels of α?subunits, which can form A-type K+ (KA) channels. METHODS Fresh dissociated L6-S1 dorsal root ganglia (DRG) neurons were prepared from female spinal intact and SCI (T9-T10 transection) SD rats. 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 prior the dissociation. Since the majority (80%) of C-fibre bladder afferent neurons are known to be sensitive to capsaicin, capsaicin-sensitive neurons were selected for evaluation. The expression levels of Kv1.2 and 1.4 α-subunits were evaluated using immunohistochemical methods. RESULTS Capsaicin-sensitive B-AN from SCI rats exhibited increased cell excitability evidenced by lower thresholds for spike activation (-26.4±1.3mV) and the increased number of action potentials (4.7±0.7 spikes) during a 800 msec depolarizing pulse compare to control rats (-21.8±0.9mV and 1.3±0.1 spikes). The peak density of 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. On the other hand, the sustained delayed-rectifier K+ current density was not altered after SCI. The expression of Kv1.4 α?subunits, which can form KA channels, was reduced in B-AN from SCI rats compared to control rats. CONCLUSIONS These results indicate that the excitability of capsaicin-sensitive C-fiber B-AN is increased in association with reductions in KA current size and Kv1.4 α-subunit expression in SCI rats. Thus, the Kv1.4 α-subunit could be a potential molecular target for treating OAB due to neurogenic detrusor overactivity. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e702-e703 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryosuke Takahashi Fukuoka, Japan 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 ...