5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular Ca^2＋ ([Ca^2＋]_i) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-HT_{2B, 3, 4, and 7} receptors in ICC. However, SDZ 205557 (a 5-HT₄ receptor antagonist), SB 269970 (a 5-HT₇ receptor antagonist), 3-tropanylindole − 3 − carboxylate methiodide (3-TCM; a 5-HT₃ antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-HT_2B receptor antagonist). Based on [Ca^2＋]_i analysis, we found that 5-HT increased the intensity of [Ca^2＋]_i. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-HT_{3, 4, and 7}receptors via [Ca^2＋]_i mobilization and regulation of mitogen-activated protein kinases.