Hyperexcitability of Bladder Afferent Neurons Associated with Reduction of Kv1.4 α-Subunit in Rats with Spinal Cord Injury

Purpose: To clarify the functional and molecular mechanisms inducing hyperexcitability of C-fiber bladder afferent pathways after spinal cord injury we examined changes in the electrophysiological properties of bladder afferent neurons, focusing especially on voltage-gated K channels. Materials and Methods: Freshly dissociated L6-S1 dorsal root ganglion neurons were prepared from female spinal intact and spinal transected (T9-T10 transection) Sprague Dawley (R) rats. Whole cell patch clamp recordings were performed on individual bladder afferent neurons. Kv1.2 and Kv1.4 alpha-subunit expression levels were also evaluated by immunohistochemical and real-time polymerase chain reaction methods. Results: Capsaicin sensitive bladder afferent neurons from spinal transected rats showed increased cell excitability, as evidenced by lower spike activation thresholds and a tonic firing pattern. The peak density of transient alpha-type K+ currents in capsaicin sensitive bladder afferent neurons from spinal transected rats was significantly less than that from spinal intact rats. Also, the K-A current inactivation curve was displaced to more hyperpolarized levels after spinal transection. The protein and mRNA expression of Kv1.4 alpha-subunits, which can form transient alpha-type K+ channels, was decreased in bladder afferent neurons after spinal transection. Conclusions: Results indicate that the excitability of capsaicin sensitive C-fiber bladder afferent neurons is increased in association with reductions in transient alpha-type K+ current density and Kv1.4 alpha-subunit expression in injured rats. Thus, the Kv1.4 alpha-subunit could be a molecular target for treating overactive bladder due to neurogenic detrusor overactivity.