title: Enhanced excitability and down-regulated voltage-gated potassium channels in colonic drg neurons from neonatal maternal separation rats.
abstract: Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy.
  
  
  CONCLUSIONS
  This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Jia-Lie
authors.initials: JL
authors.lastname: Luo
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Chun-Kit
authors.initials: CK
authors.lastname: Wong
authors.forename: Suk-Ying
authors.initials: SY
authors.lastname: Tsang
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhao-Xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000294:innervation* / Q000378:metabolism; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D008297:Male; D008426:Maternal Deprivation; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D024642:Potassium Channels, Voltage-Gated