Decreased potassium channel IK1 and its regulator neurotrophin-3 (NT-3) in inflamed human bowel

Calcium-activated potassium currents of intermediate conductance (IKI) have been described in the rodent enteric nervous system, where they may regulate afterhyperpolarisation of intrinsic primary afferent neurons. Using specific antibodies for immunocytochemistry, we now report IKI-like immunoreactivity for the first time in enteric neurons of human colon, and a significant decrease of IKI-positive cells in myenteric plexus in inflamed colon from patients with Crohn's disease and ulcerative colitis (p=0.031). Neurotrophin-3 (NT-3), which regulates IKI expression, was also observed in fewer neurons of the myenteric ganglia in Crohn's bowel (p=0.048), and in inflamed colonic extracts by Western blotting (p=0.004); the numbers of neurons expressing the NT-3 high affinity receptor trk C were unchanged. Our findings may explain the diarrhoea and colicky abdominal pain produced by inflammatory bowel disease, and by IKI-blocking pyridine drugs prescribed for neuromuscular disorders.