PURPOSE: The pathophysiology of Hirschsprung's disease (HSCR) is not entirely 
understood. There is no clear explanation for the occurrence of the spastic or 
tonically contracted aganglionic segment of bowel. Kv11.1 (hERG) channels play a 
critical role in the regulation of the resting membrane potential as well as 
affecting either the force or frequency of contraction of smooth muscles. We 
designed this study to investigate the expression and distribution of hERG 
channels in the normal colon and the colon of patients with HSCR.
METHODS: We investigated hERG protein expression in both the ganglionic and 
aganglionic regions of HSCR patients (n = 10) versus normal control colon 
(n = 10). Protein distribution was assessed using immunofluorescence and 
confocal microscopy. Gene and protein expressions were quantified using 
real-time polymerase chain reaction, western blot analysis and densitometry.
RESULTS: Confocal microscopy of the normal colon revealed strong hERG channel 
expression in interstitial cells of Cajal, platelet-derived growth factor-alpha 
receptor- (PDGFRα(+)) positive cells and enteric neurons. hERG expression was 
markedly decreased in aganglionic bowel, whereas colonic hERG gene expression 
levels were significantly decreased in aganglionic compared to ganglionic bowel 
and controls (p < 0.05). Western blotting revealed decreased colonic hERG 
protein expression in aganglionic HSCR specimens compared to controls.
CONCLUSIONS: We demonstrate, for the first time, the expression and distribution 
of hERG channels in the human colon. The decreased expression of hERG in the 
aganglionic colon may be responsible for the increased tone in the aganglionic 
narrow spastic segment of bowel.