Interstitial cells of Cajal (ICCs) are pacemaker cells that control smooth muscle contraction in the gastrointestinal (GI) tract. The present study investigated the effects of Salvia miltiorrhiza (SM) on the pacemaker potentials of ICCs from the mouse small intestine in vitro and on GI motility in vivo. The whole‑cell patch‑clamp configuration was used to record pacemaker potential in ICCs in vitro, and GI motility was investigated in vivo by recording intestinal transit rate (ITR). Using the whole‑cell patch‑clamp configuration, SM depolarized the pacemaker potentials of ICCs in a dose‑dependent manner. Fulvestrant blocked SM‑induced effects but 1,3‑dihydro‑3,3‑bis(4‑hydroxyphenyl)-7-methyl‑2H‑indol‑2‑one did not. Additionally, 4‑[2‑phenyl-5,7‑bis(trifluoromethyl) pyrazolo[1,5‑a]pyrimidin‑3‑yl] phenol blocked SM‑induced effects. Intracellular guanosine 5'‑O‑(2‑thiodiphosphate), and pretreatment with extracellular Ca2+‑ and Na+‑free solutions also blocked SM‑induced effects. Furthermore, ITR values were increased by SM in vivo and SM elevated the levels of motilin (MTL). The SM‑induced increase in ITR was associated with increased protein expression levels of c‑kit and the transmembrane protein 16A (TMEM16A) channel. In addition, SM induced pacemaker potential depolarization through estrogen receptor β in a G protein‑dependent manner via extracellular Ca2+ and Na+ regulation in the murine small intestine in vitro. Moreover, SM increased the ITR in vivo through the MTL hormone via c‑kit and TMEM16A‑dependent pathways. Taken together, these results suggested that SM may have the ability to control GI motility and could be used as a GI motility regulator.
Keywords: Salvia miltiorrhiza; interstitial cells of Cajal; pacemaker potential; gastrointestinal motility; intestinal transit rate.