## 4 Discussion  
In this study, we investigated the effect of JYGCT on the pacemaker potential in the ICC obtained from the murine small intestine. JYGCT inhibited the pacemaker potential via KATP, the TRPV1, the cAMP pathway, and intracellular Ca2+ regulation, indicating that JYGCT can affect the ICC and may be a novel profinetic agent in the GI tract. JYGCT is a traditional medicine for various purposes [10]. It has been applied to treat various disease conditions; it has been used in the prevention of muscle cramps and the inhibition of skeletal muscle contractions [7], uric acid reduction, autonomic function regulation [9], and intestinal smooth muscle relaxation [25]. JYGCT has the function of decreasing the neuropathy [3] and shows an anti-inflammatory effect [1]. It also has antispasmodic effect on skeletal muscle [8], reduces the serum uric acid levels, and increases the sympathetic activities [9]. However, although JYGCT has been used as an herbal remedy to regulate the GI tract [11; 12], its regulation of GI motility has not yet been reported. In this study, we demonstrated that JYGCT modulated the pacemaker potential in the ICC. Therefore, it can be suggested that JYGCT may regulate GI motility via its effects on the ICC pacemaker potential. In a forthcoming study, we plan to investigate the effects of JYGCT's components, Jakyak and Gamcho, on the pacemaker potential in the ICC. Ion channels are important in the physiological control of GI motility [26]. Among the various ion channels, KATP channels are enriched at various locations in the GI tissues [27; 28]. KATP channels in the ICC are composed of SUR2B and Kir 6.2 in the small intestine and SUR2B and Kir 6.1 in the colon [29]. Previous studies have shown that KATP channels exist in cultured murine small intestinal ICC and reduce GI motility by causing relaxation of the smooth muscles; this makes them potential candidates in the treatment of GI motor diseases [30]. In addition, the TRPV1 channels are expressed throughout the alimentary canal where they play important roles in GI motility through the ICC [18]. Various studies show that the TRPV1 channels are involved in the treatment of gastric esophageal reflux disease and GI pain hypersensitivity in the GI tract [18; 31]. In this study, JYGCT inhibited the pacemaker potential in the ICC via KATP (Figure 2) and the TRPV1 (Figure 3). Therefore, we believe that KATP and the TRPV1 channels may get involved in the JYGCT-induced inhibition of pacemaker potential. Next, we intend to study  
Figure 6: Effects of JYGCT on zymosan-induced colonic changes. (**A**) Colon length; (**B**) Colon weight; (**C**) Stool scores were analyzed. Bars represents the mean \(\pm\) SE. \({}^{*}p<0.05\). \(\#\)\(p<0.05\). \(\#\)\(p<0.0001\). \(\#\)\(\#\)\(p<0.0001\). \(\#\  
the specific processes and molecular control strategies of KATP and the TRPV1 channels in the ICC. The intracellular regulation of Ca2+ flux has a role in the pacemaker activity in the ICC [24; 32]. Ca2+ flux regulation is important for generating the pacemaker activity in the ICC [33]. In the present study, spontaneous [Ca2+]i responses were inhibited by JYGCT (Figure 5). Therefore, we concluded that JYGCT inhibited the pacemaker potential and probably regulates the pacemaker activity through intracellular Ca2+ modulations. In addition, three cell surface proteins, TRPM7, c-Kit, and TMEM16A, are used for identifying the ICCs activation [15; 22; 23; 24]. In this study, JYGCT increased the ITR and the expression of TMEM16A was only increased by JYGCT, but the expression of c-Kit and TRPM7 was not (Figure 5A,B). In addition, we looked at changes in GI hormones. GI hormonal changes can alter GI motility [34; 35]. The roles of GI hormones are diverse and extensive, and although not fully understood yet, they are known to have a significant impact on the physiological functions of the GI tract [36]. In particular, it is known that hormones are responsible for regulating the process of food being digested and sent down through the GI tract [37].