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Transient Receptor Potential Canonical 4 and 5 Channel Antagonist ML204 Depolarized Pacemaker Potentials of Interstitial Cells of Cajal

Journal of Neurogastroenterology and Motility 2020년 26권 4호 p.521 ~ 528
이준형, Wu Wen-Hao, Huang Xing-You, 전제열, Choi Seok,
소속 상세정보
이준형 ( Lee Jun-Hyung ) - Chosun University School of Medicine Department of Internal Medicine
 ( Wu Wen-Hao ) - Chosun University School of Medicine Department of Physiology
 ( Huang Xing-You ) - Chosun University School of Medicine Department of Physiology
전제열 ( Jun Jae-Yeoul ) - Chosun University School of Medicine Department of Physiology
 ( Choi Seok ) - Chosun University School of Medicine Department of Physiology

Abstract


Background/Aims: To investigate an effect of ML204 (an inhibitor of transient receptor potential canonical 4 and 5 [TRPC4/5] channels) on interstitial cells of Cajal (ICCs) and therefore determine whether TRPC4/5 channels act on ICC-generated pacemaker activity.

Methods: We enforced whole cell patch clamp analysis, measurements of the intracellular Ca2+ concentration, and reverse transcription polymerase chain reaction to determine the effect of ML204 (10 μM) or englerin A (a selective activator of TRPC4/5 channeles, 10 μM) and the existence of TRPC4/5 in mouse small intestinal ICC.

Results: Treatment of ICCs with ML204 or englerin A caused the membrane potentials to depolarize. This depolarization effect of membrane potentials by ML204 in ICCs was observed to be concentration-dependent. After treating Ca2+- and Na+-free solutions or flufenamic acid (a non-selective cation channel blocker), the pacemaker potentials in the ICCs were abolished. A specific anoctamin 1 channel blocker did not have any effect on the pacemaker activity in ML204-untreated control cells; however, they blocked ML204-induced pacemaker activity in ICCs. Specific primers designed against TRPC4 and TRPC5 detected the presence of TRPC4/5 in small intestinal ICCs, and the application of ML204 increased raise the frequency of Ca2+ oscillations in ICCs, as assessed using Fluo-4 AM.

Conclusion: The results implied that ML204 could not inhibit the pacemaker activity but depolarized the membrane potential of ICCs by regulating intracellular Ca2+ oscillations and anoctamin 1 channels.

키워드

Anoctamin-1; Interstitial cells of Cajal; Membrane potentials; TRPC cation channels

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