Acceleration of ileal pacemaker activity in mice lacking interleukin 10

Epidemiological studies indicate the genetic association between irritable bowel syndrome and inflammatory bowel disease, including genetic mutations related with interleukin 10 (IL-10), serotonin, and so on. On the other hand, it becomes clearer that interstitial cells of Cajal (ICC) play a major role in gut motility by coordinating the electric activity of cellular members and generating pacemaker potentials. Ileal musculatures containing the myenteric plexus and ICC were isolated from wild-type (WT) and IL-10-deficient mice. A microelectrode array system was used to simultaneously measure 8 × 8 field potentials over a ∼1 mm area. Nifedipine and tetrodotoxin were applied to predominantly evaluate ICC electric activity. Histological changes were also assessed by immunohistochemistry. Potential mapping revealed that spontaneous electric activity was synchronized throughout the recording area in ileal musculature preparations of both WT and IL-10-deficient mice, but rapid propagation was observed in the latter. The spectral power in the frequency range of 9.4 to 30.0 cpm (Pw9.4-30.0) did not differ between these preparations, but the oscillation frequency estimated using autocorrelation analysis was significantly higher in IL-10-deficient mice than in WT mice (22.16 ± 4.10 versus 15.72 ± 1.61 cpm). In immunohistochemistry, no significant changes were observed in ICC, macrophages, and enteric neurons in the ileum of WT and IL-10-deficient mice. This study provides evidence for accelerated pacemaker activity in the ileum of IL-10-deficient mice, not accompanied by any significant histological changes. This could be accounted, as an example, by a genetic cross-link between inflammatory bowel disease and irritable bowel syndrome.