Rebound excitation and alternating slow wave patterns depend upon eicosanoid production in canine proximal colon.

Abstract

1. We tested the hypothesis that eicosanoid production could be related to the long-duration slow waves that occur after brief periods of inhibitory neurotransmission (rebound excitation) and the alternating patterns of long- and short-duration slow waves observed in the canine proximal colon. 2. Electrical field stimulation of colonic muscles inhibited slow waves during the stimulus and a long-duration slow wave occurred after the stimulus. Indomethacin reduced the post-stimulus response without affecting the inhibitory response. 3. ATP or 2-methylthio-ATP produced post-stimulus rebound responses similar to the response to field stimulation. Indomethacin inhibited the rebound response caused by ATP or 2-methylthio-ATP. 4. Alternating patterns consisting of long- and short-duration slow waves occurred spontaneously in some colonic muscles. These patterns could also be induced with acetylcholine. 5. Indomethacin, acetylsalicylic acid and ibuprofen abolished the alternating pattern and shifted the bimodal distribution of slow wave durations toward an intermediate duration. 6. Patch clamp experiments on isolated colonic myocytes showed that indomethacin blocked L-type Ca2+ currents. The effects of indomethacin on rebound excitation and alternating slow waves were accomplished at concentrations that blocked cyclooxygenase activity without significantly inhibiting L-type Ca2+ currents. 7. The results demonstrate that rebound excitation and alternating slow wave patterns in the canine colon have similar dependence on endogenous eicosanoid production. Rebound excitation may result from reduced production of an inhibitory eicosanoid during inhibitory nerve stimulation, and the alternating pattern may result from oscillations in eicosanoid production as a function of changes in cytoplasmic Ca2+ during long and short slow waves.