Nitric oxide (NO) and adenosine triphosphate (ATP) mediate smooth muscle relaxation in the GI tract. However, the involvement of these neurotransmitters in spontaneous neuronal activity is unknown. The aim of the present work was to study spontaneous neuromuscular transmission in the rat mid colon. Microelectrode experiments were performed under constant stretch both in circular and longitudinal directions. Spontaneous inhibitory junction potentials (sIJP) were recorded. Tetrodotoxin (TTX) 1 µM and apamin 1µM depolarized smooth muscle cells and inhibited sIJP. Nω-nitro-L-arginine (L-NNA) 1 mM depolarized smooth muscle cells but did not modify sIJP. In contrast, the P2Y1 antagonist MRS2500 1µM did not modify the resting membrane potential (RMP) but reduced sIJP (IC50 = 3.1 nM). Hexamethonium 200 µM, NF023 10 µM and Ondansetron 1 µM did not modify RMP and sIJP. These results correlate with in vitro (muscle bath) and in vivo (strain gauges) data where L-NNA but not MRS2500 induced a sustained increase of spontaneous motility. We concluded that in the rat colon, inhibitory neurons regulate smooth muscle RMP and cause sIJP. In vitro, the release of inhibitory neurotransmitters is independent of Nicotinic, P2X and 5-HT3 receptors. Neuronal NO causes a sustained smooth muscle hyperpolarization that is responsible for a constant inhibition of spontaneous motility. In contrast, ATP acting on P2Y1 receptors is responsible for sIJP but does not mediate inhibitory neural tone. ATP and NO have complementary physiological functions in the regulation of GI motility.
- junction potential
- Copyright © 2009, American Journal of Physiology- Gastrointestinal and Liver Physiology