Abstract
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 Nav1.9 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 Nav1.9 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 Nav1.9 null mice. Spontaneous CMMCs were observed in all preparations. The mean frequency of CMMCs was significantly higher in the Nav1.9 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 Nav1.9 null mice compared to the wild type. In addition, CMMCs propagated preferentially in an aboral direction in the Nav1.9 null mice. Our study demonstrates that CMMCs do occur in mice lacking the Nav1.9 channel, but their characteristics are significantly different from controls. Up to now, the Nav1.9 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 Nav1.9 channel in a complex colonic motor pattern.
Highlights
Sodium (Na+) channels are essential for action potential generation and propagation in nerve cells
It was found that 31.5% of myenteric neurons that were immunoreactive for Nav1.9 were immunoreactive to NF-200
The present study shows that in vitro colonic migrating motor complex (CMMC) are present in mice lacking Nav1.9, there are some major differences in their characteristics when compared to control mice
Summary
Sodium (Na+) channels are essential for action potential generation and propagation in nerve cells. Because of its slow activation kinetics, this TTXr Na+ current is probably not substantially involved in the generation of action potentials. Rather, it may set the resting membrane potential, determine the shape of the action potential and tune the voltage threshold for the firing of action potentials (Dib-Hajj et al, 2002; Coste et al, 2004; Rogers et al, 2006; Cummins et al, 2007; Maingret et al, 2008). Any change in excitability of enteric sensory neurons may shape their integrative properties and affect gut motility and secretion
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