Regulation of Intracellular Calcium by Endoplasmic Reticulum Proteins in Small Intestinal Interstitial Cells of Cajal
- Author:
Chan Guk PARK
1
;
Mei Jin WU
;
Chansik HONG
;
Ju Yeon JO
;
Han Yi JIAO
;
Hyun PARK
;
Jae Yeoul JUN
;
Seok CHOI
Author Information
- Publication Type:Original Article
- Keywords: Interstitial cells of Cajal; Intestinal motility; Stromal interaction molecule 1; Store-operated calcium entry-associated regulatory factor
- MeSH: Animals; Calcium; Carbachol; Endoplasmic Reticulum; Gadolinium; Gastrointestinal Motility; Gastrointestinal Tract; Interstitial Cells of Cajal; Intestine, Small; Ions; Membranes; Mice
- From:Journal of Neurogastroenterology and Motility 2018;24(1):128-137
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: We investigated the role of representative endoplasmic reticulum proteins, stromal interaction molecule 1 (STIM1), and store-operated calcium entry-associated regulatory factor (SARAF) in pacemaker activity in cultured interstitial cells of Cajal (ICCs) isolated from mouse small intestine. METHODS: The whole-cell patch clamp technique applied for intracellular calcium ions ([Ca²+]i) analysis with STIM1 or SARAF overexpressed cultured ICCs from mouse small intestine. RESULTS: In the current-clamping mode, cultured ICCs displayed spontaneous pacemaker potentials. External carbachol exposure produced tonic membrane depolarization in the current-clamp mode, which recovered within a few seconds into normal pacemaker potentials. In STIM1-overexpressing cultured ICCs pacemaker potential frequency was increased, and in SARAF-overexpressing ICCs pacemaker potential frequency was strongly inhibited. The application of gadolinium (a non-selective cation channel inhibitor) or a Ca2+-free solution to understand Orai channel involvement abolished the generation of pacemaker potentials. When recording intracellular Ca²+ concentration with Fluo 3-AM, STIM1-overexpressing ICCs showed an increased number of spontaneous intracellular Ca²+ oscillations. However, SARAF-overexpressing ICCs showed fewer spontaneous intracellular Ca2+ oscillations. CONCLUSION: Endoplasmic reticulum proteins modulated the frequency of pacemaker activity in ICCs, and levels of STIM1 and SARAF may determine slow wave patterns in the gastrointestinal tract.