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 (IA) and delayed rectifier (IK) K+ currents. Compared with NH rat neurons, the averaged density of IK 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 IK current, which is likely accounted for by the downregulation of the Kv1.2 expression
and somal hypertrophy.
Perspective
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.
Key words
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Article info
Publication history
Published online: February 07, 2011
Accepted:
November 23,
2010
Received in revised form:
October 26,
2010
Received:
May 19,
2010
Footnotes
Supported by Research Grants Council Hong Kong (HKBU 260008).
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
