J Neurogastroenterol Motil  
Regulation of Intracellular Calcium by Endoplasmic Reticulum Proteins in Small Intestinal Interstitial Cells of Cajal
Chan Guk Park,1 Mei Jin Wu,2 Chansik Hong,2 Ju Yeon Jo,1 Han Yi Jiao,2 Hyun Park,3 Jae Yeoul Jun,2 and Seok Choi2*
1Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea 2Department of Medicine, Graduate School, Chosun University, Gwangju, Korea and 3Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
Correspondence to: Seok Choi, PhD
Department of Physiology, College of Medicine, Chosun University, 309, Pilmun-daero, Dong-gu, Gwangju 61452, Korea
Tel: +82-62-230-6413, Fax: +82-62-232-4943, E-mail: choiseok@chosun.ac.kr
*Chan Guk Park and Mei Jin Wu contributed equally to this work.
Received: December 13, 2016; Revised: March 13, 2017; Accepted: April 7, 2017; Published online: August 4, 2017.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Interstitial cells of Cajal; Intestinal motility; Stromal interaction molecule 1; Store-operated calcium entry-associated regulatory factor


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