Effects of Ca2+-Activated Cl- Channel ANO1inhibitors on Pacemaker Activity in Interstitial Cells of Cajal
Autor: | Chansik Hong, Hyun Goo Kang, Dong Hoon Shin, Jae Yeoul Jun, Mei Jin Wu, Han Yi Jiao, Seok Choi |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Patch-Clamp Techniques Physiology Colon ANO1 Thiophenes lcsh:Physiology Membrane Potentials lcsh:Biochemistry 03 medical and health sciences symbols.namesake Pacemaker potential chemistry.chemical_compound Mice Ca2+-activated Cl- channel medicine Animals ortho-Aminobenzoates lcsh:QD415-436 Anoctamin-1 Cells Cultured Gastrointestinal tract Mibefradil Mice Inbred BALB C biology lcsh:QP1-981 Chemistry Molecular biology Small intestine Interstitial cell of Cajal Thiazoles 030104 developmental biology medicine.anatomical_structure Pyrimidines DIDS Interstitial cells of Cajal symbols biology.protein Calcium Female T-type Ca2+ channel Intracellular medicine.drug |
Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 6, Pp 2887-2899 (2018) |
ISSN: | 1421-9778 1015-8987 |
Popis: | Background/Aims: Anoctamin1 (Ca2+-activated Cl- channel, ANO1) is a specific marker of the interstitial cells of Cajal (ICC) in the gastrointestinal tract, and are candidate proteins that can function as pacemaker channels. Recently, novel selective ANO1 inhibitors were discovered and used to study Ca2+-activated Cl- channels. Therefore, to investigate whether ANO1 channels function as pacemaker channels, selective ANO1 inhibitors were tested with respect to the pacemaker potentials in ICC. Methods: Whole-cell patch-clamp recording, RT-PCR, and intracellular Ca2+ ([Ca2+]i) imaging were performed in cultured ICC obtained from mice. Results: Though CaCCinh-A01 (5 µM), T16Ainh-A01 (5 µM), and MONNA (5 µM) (selective ANO1 inhibitors) blocked the generation of pacemaker potentials in colonic ICC, they did not do so in small intestinal ICC. Though nifulmic acid (10 µM) and DIDS (10 µM) (classical Ca2+-activated Cl- channel inhibitors) also had no effect in small intestinal ICC, they suppressed the generation of pacemaker potentials in colonic ICC. In addition, knockdown of ANO1 reduced the pacemaker potential frequency in colonic ICC alone. Though ANO1 inhibitors suppressed [Ca2+]i oscillations in colonic ICC, they did not do so in small intestinal ICC. T-type Ca2+ channels were expressed in the both the small intestinal and colonic ICC, but mibefradil (5 µM) and NiCl2 (30 µM) (T-type Ca2+ channel inhibitors) inhibited the generation of pacemaker potentials in colonic ICC alone. Conclusion: These results indicate that though ANO1 and T-type Ca2+ channels participate in generating pacemaker potentials in colonic ICC, they do not do so in small intestinal ICC. Therefore, the mechanisms underlying pacemaking in ICC might be different in the small intestine and the colon. |
Databáze: | OpenAIRE |
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