Basic Science PaperDecreased expression of Kv7 channels in Hirchsprung's disease
Section snippets
Tissue samples
This study was approved by the Ethics Medical Research Committee, Our Lady's Children's Hospital, Dublin, Ireland (Ref. GEN/292/12) and tissue samples were obtained with informed parental consent. HSCR specimens from 10 patients who underwent pull-through surgery were studied. These specimens were divided into aganglionic and ganglionic samples. HD patients were aged 6 ± 3 months old. We compared the most distal aganglionic segments with the most proximal ganglionic segments. Normal control colon
Immunofluorescence staining and confocal microscopy
Immunofluorescence double-staining revealed that Kv7.3 and Kv7.4 were expressed in Hu-positive neurons located within both the myenteric and submucosal plexuses of the normal human colon, as well as in ICCs in the both the myenteric plexus and in the smooth muscle layer (Fig. 1). Kv7.5 was found to be expressed on both ICCs and SMCs in the normal human colon (Fig. 2). A decreased expression of Kv7.4 was observed within both the ganglionic and aganglionic tissue specimens, while Kv7.3 and Kv7.5
Discussion
K+ channels play important roles in excitable cells, neurons and SMCs, in which they are involved in several physiological processes, such as action potential firing, neurotransmitter release and smooth muscle contractility [5]. The cell membrane potential hyperpolarizes whenever K+ channels open, as K+ flows out of the cell due to the large transmembrane electrochemical gradient, and cell excitability decreases. In the smooth muscle, this results in a reduction of contractility, that is mainly
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Translational research in Hirschprung’s disease at the National Children’s Research Centre in Dublin
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