Decreased Na_v1.9 channel expression in Hirschsprung's disease

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• 作者：Anne-Marie O'Donnell ; David Coyle ; Prem Puri ; ^{prem.puri@ucd.ie" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nav1.9 ; Voltage-gated sodium channels ; Enteric nervous ; Hirschsprung's disease
• 刊名：Journal of Pediatric Surgery
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：51
• 期：9
• 页码：1458-1461
• 全文大小：819 K

文摘

Voltage-gated sodium channel subtype 9 (Na_v1.9) are expressed in dorsal root ganglion neurons and are known to be involved in pain during inflammation. Animal studies have reported Na_v1.9 channel expression in myenteric intrinsic primary afferent neurons (IPANs). More recently, a study involving Na_v1.9 knockout mice showed clear evidence of colonic dysmotility. However, there are no data regarding the expression of these channels in the human intestine, thus, the aim of our study was to determine Na_v1.9 channel expression within the human colon and to elucidate if Na_v1.9 channel expression is altered in Hirschsprung's disease (HD).

Methods

HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while normal controls were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Na_v1.9 immunofluorescence was visualized using confocal microscopy to assess the distribution of the protein. Western blot analysis was undertaken to determine Na_v1.9 protein quantification.

Results

Confocal microscopy revealed Na_v1.9-immunoreactive neurons within the submucosal and myenteric plexus in normal controls, with a reduction in the HD specimens. Calbindin double-labeling showed that Na_v1.9-immunoreactive neurons were IPANs. Na_v1.9 channels were also seen to be co-localized on smooth muscle cells in all tissues. Western blotting revealed high levels of Na_v1.9 protein expression in normal controls, while there was a marked decrease in Na_v1.9 protein expression in the HD tissue.

Conclusion

Our results show the expression of Na_v1.9 channels within the human colon for the first time. Furthermore, Na_v1.9 channel expression is decreased in HD versus normal controls.