P84 H2S inhibits NO generation and this inhibition contributes to H2S-induced muscle contraction in mouse colon smooth muscle

Abstract

H 2 S is generated by CSE in the muscle layers of the mouse colon. The aim of this study was to study the effect of H 2 S on mouse colon circular smooth muscle cells and investigate a possible link between changes in the electrical activity and the muscle tone. Result: Superfusion of NaHS (0.2 mM) had no significant effect on resting membrane potential but inhibited ongoing myoelectric complexes of muscle cells and induced a biphasic change in muscle tone: initial muscle contraction followed by relaxation. Washing out NaHS restored the ongoing myoelectric complexes but did not restore resting muscle tone suggesting that relaxation was not associated with electric activity of smooth muscle cells. NaHS reduced the frequency and amplitude of spontaneous inhibitory junction potentials (IJPs) with a time course similar to muscle contraction. Also, NaHS reduced NO-mediated slow-IJPs evoked by field stimulation suggesting H 2 S inhibits NO production. We further tested NO generation in wild type and CSE-KO mouse preparations. Both tissue levels of NO and the amplitude of evoked slow-IJPs were significantly higher in muscle layers of CSE-KO mice. Our results suggest that the action of H 2 S on colonic smooth muscle cell physiology involving brief contraction and irreversible relaxation, inhibition of myoelectrical activity, and inhibition of NO likely occurs via three independent mechanisms. The inhibition of NO contributes to the H 2 S-induced muscle contraction phase (Support: NIH DK17238).