Distribution of Ca2+-activated K channels, SK2 and SK3, in the normal and Hirschsprung's disease bowel.

PURPOSE: The aim of this study was to investigate the expression and distribution of SK2 and SK3 channels in the normal and Hirschsprung's disease (HD) bowel.

METHODS

Full-thickness colonic specimens were collected at pull-through operation from 10 patients with HD and from 6 patients during bladder augmentation. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for SK2 and SK3 channels and double immunostaining using anti SK2/c-kit, SK3/c-kit, SK2/alpha-SMA, and SK2/PGP 9,5 antibodies was performed. Immunolocalization was detected using laser scanning microscopy.

RESULTS

RT-PCR analysis showed strong expression of SK2 and SK3 mRNA in the normal human bowel and significantly reduced SK3 expression in the aganglionic bowel (P <.05). In the normal colon, double labeling immunohistochemistry showed strong SK3 immunoreactivity (IR) colocalizing in the c-kit-positive ICCs. In the aganglionic bowel, SK3 IR was reduced markedly in the sparsely found ICCs. There was strong SK2 IR mainly in smooth muscles in the normal and aganglionic bowel.

CONCLUSIONS

The results of this study provide the first evidence for the presence of SK2 and SK3 channels and for the immunocolocalization of SK3 channels in the ICCs in the normal human colon. Decreased expression SK3 channels in the aganglionic bowel may contribute to motility dysfunction in HD.