• ChAT;
  • gastrointestinal tract;
  • HCN2;
  • interstitial cells of Cajal;
  • myenteric plexus


HCN2 channels are involved in the spontaneous rhythmic activities of some CNS neurons and act by generating If current. The gastrointestinal (GI) tract is known to be capable of spontaneous rhythmic activity; however, the possible role of HCN2 channels in this organ has not yet been elucidated. This study investigated the distribution of HCN2-positive cells in the mouse GI tract using immunohistochemistry. To identify the nature of these HCN2 cells, anti-ChAT and anti-Kit antibodies were used to co-label neurons and the interstitial cells of Cajal (ICCs), respectively. Additionally, differences in the distribution of HCN2-positive cells within the GI tract were also analyzed. Our results showed that HCN2 channels were mainly located within the myenteric neurons of the enteric nervous system in the GI tract. Double-staining revealed that HCN2-positive neurons were labeled by ChAT, indicating that these HCN2-positive cells are also cholinergic neurons. Although the HCN2-positive cells were not stained by the anti-Kit antibody, their processes were in close proximity to ICCs around the myenteric plexus region. Moreover, several differences in the distribution of HCN2 in the stomach, small intestine and colon were partly consistent with the regional differences in the spontaneous rhythmic activities of these organs. Basing on the role HCN2, we suggested that HCN2 channels facilitate the release of Ach from cholinergic neurons to affect the GI peristalsis by acting on M receptors on the ICCs. However, the HCN2 channels are not directly involved in spontaneous slow-wave initiation by ICCs.