The Na(v)1.9 channel regulates colonic motility in mice

The colonic migrating motor complex (CMMC) is a major pattern of motility that is entirely generated and organized by the enteric nervous system. We have previously demonstrated that the Na(v)1.9 channel underlies a tetrodotoxin-resistant sodium current which modulates the excitability of enteric neurons. The aim of this study was to observe the effect of loss of the Na(v)1.9 channel in enteric neurons on mouse colonic motility in vitro. The mechanical activity of the circular muscle was simultaneously recorded from three sites, namely, proximal, mid- and distal, along the whole colon of male, age-matched wild-type and Na(v)1.9 null mice. Spontaneous CMMCs were observed in all preparations. The mean frequency of CMMCs was significantly higher in the Na(v)1.9 null mice (one every 2.87 ± 0.1 min compared to one every 3.96 ± 0.23 min in the wild type). The mean duration of CMMCs was shorter and the mean area-under-contraction was larger in the Na(v)1.9 null mice compared to the wild type. In addition, CMMCs propagated preferentially in an aboral direction in the Na(v)1.9 null mice. Our study demonstrates that CMMCs do occur in mice lacking the Na(v)1.9 channel, but their characteristics are significantly different from controls. Up to now, the Na(v)1.9 channel was mainly associated with nociceptive neurons and involved in their hyperexcitability after inflammation. Our result shows for the first time a role for the Na(v)1.9 channel in a complex colonic motor pattern.