title: Hyperexcitability of bladder afferent neurons associated with reduction of Kv1.4 α-subunit in rats with spinal cord injury.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Freshly dissociated L6-S1 dorsal root ganglion neurons were prepared from female spinal intact and spinal transected (T9-T10 transection) Sprague Dawley® rats. Whole cell patch clamp recordings were performed on individual bladder afferent neurons. Kv1.2 and Kv1.4 α-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 A-type K+ currents in capsaicin sensitive bladder afferent neurons from spinal transected rats was significantly less than that from spinal intact rats. Also, the KA current inactivation curve was displaced to more hyperpolarized levels after spinal transection. The protein and mRNA expression of Kv1.4 α-subunits, which can form transient A-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 A-type K+ current density and Kv1.4 α-subunit expression in injured rats. Thus, the Kv1.4 α-subunit could be a molecular target for treating overactive bladder due to neurogenic detrusor overactivity.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yunoki
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D005260:Female; D051665:Kv1.4 Potassium Channel / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D001743:Urinary Bladder / Q000294:innervation* / Q000503:physiopathology*
chemical_list: D051665:Kv1.4 Potassium Channel
keywords: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; A-type K(+); DRG; DTX; DiI; FITC; GAPDH; K(A); K(DR); Kv; NDO; PBS; PCR; SCI; TTX; V(h); afferent pathways; delayed rectifier-type K(+); dorsal root ganglion; fluorescein isothiocyanate; glyceraldehyde-3-phosphate dehydrogenase; half-maximal conductance; nerve fibers; neurogenic detrusor overactivity; overactive; phosphate buffered saline; polymerase chain reaction; potassium channels; spinal cord injuries; spinal cord injury; tetrodotoxin; unmyelinated; urinary bladder; voltage-gated; voltage-gated K(+); α-dendrotoxin
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 May;296(5):R1661-70
references.pmid: 19279288
references.citation: J Neurosci. 2006 Oct 18;26(42):10847-55
references.pmid: 17050722
references.citation: J Pharmacol Exp Ther. 1998 Jun;285(3):1051-60
references.pmid: 9618407
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13373-8
references.pmid: 11698689
references.citation: Prog Brain Res. 2006;152:59-84
references.pmid: 16198694
references.citation: J Physiol. 1997 Sep 1;503 ( Pt 2):269-76
references.pmid: 9306271
references.citation: J Neurophysiol. 1999 Aug;82(2):700-8
references.pmid: 10444667
references.citation: J Neurophysiol. 1996 Jun;75(6):2629-46
references.pmid: 8793767
references.citation: Neuroscience. 2004;123(4):867-74
references.pmid: 14751280
references.citation: J Neurosci. 1999 Jun 1;19(11):4644-53
references.pmid: 10341262
references.citation: J Physiol. 1996 Jul 1;494 ( Pt 1):1-16
references.pmid: 8814602
references.citation: Circ Res. 1993 Jun;72(6):1326-36
references.pmid: 8495559
references.citation: Nature. 1991 Mar 21;350(6315):232-5
references.pmid: 1706481
references.citation: J Auton Nerv Syst. 1995 Sep 5;54(3):215-24
references.pmid: 7490423
references.citation: Neuroscience. 1998 Mar;83(2):633-43
references.pmid: 9460769