We studied whether nitric oxide (NO) and hydrogen sulfide (H(2)S) have an interaction on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of NO and H(2)S on pacemaker activities were investigated by using the whole-cell patch-clamp technique and intracellular Ca(2+) analysis at 30℃ in cultured mouse ICC. Exogenously applied (±)-S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, or sodium hydrogen sulfide (NaHS), a donor of H(2)S, showed no influence on pacemaker activity (potentials and currents) in ICC at low concentrations (10 µM SNAP and 100 µM NaHS), but SNAP or NaHS completely inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction at high concentrations (SNAP 100 µM and NaHS 1 mM). Co-treatment with 10 µM SNAP plus 100 µM NaHS also inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction. ODQ, a guanylate cyclase inhibitor, or glibenclamide, an ATP-sensitive K(+) channel inhibitor, blocked the SNAP+NaHS-induced inhibition of pacemaker currents in ICC. Also, we found that SNAP+NaHS inhibited the spontaneous intracellular Ca(2+) ([Ca(2+)](i)) oscillations in cultured ICC. In conclusion, this study describes the enhanced inhibitory effects of NO plus H(2)S on ICC in the mouse small intestine. NO+H(2)S inhibited the pacemaker activity of ICC by modulating intracellular Ca(2+). These results may be evidence of a physiological interaction of NO and H(2)S in ICC for modulating gastrointestinal motility.
Keywords: Hydrogen sulfide; Interstitial cells of Cajal (ICC); Intestinal motility; Nitric Oxide; Pacemaker currents.