Effects of Dangkwisoo‑san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal

Sung,Soon‑Ki; Kim,Sung  Jin; Ahn,Tae  Seok; Hong,Noo  Ri; Park,Hyun  Soo; Kwon,Young  Kyu; Kim,Byung  Joo

doi:10.3892/mmr.2015.4203

Effects of Dangkwisoo‑san, a traditional herbal medicine for treating pain and blood stagnation, on the pacemaker activities of cultured interstitial cells of Cajal

Authors:
- Soon‑Ki Sung
- Sung Jin Kim
- Tae Seok Ahn
- Noo Ri Hong
- Hyun Soo Park
- Young Kyu Kwon
- Byung Joo Kim
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Affiliations: Department of Neurosurgery, Pusan National University, Yangsan Hospital, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea, Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea
Published online on: August 10, 2015 https://doi.org/10.3892/mmr.2015.4203
Pages: 6370-6376

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Abstract

The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of Dangkwisoo‑san (DS) on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole‑cell patch‑clamp configuration was used to record pacemaker potentials from cultured ICCs and the increase in intracellular Ca2+ concentration ([Ca2+i) was analyzed in cultured ICCs using fura‑2‑acetoxymethyl ester. The generation of pacemaker potentials in the ICCs was observed. DS produced pacemaker depolarizations in a concentration dependent manner in current clamp mode. The 4‑diphenylacetoxy‑N‑methyl‑piperidine methiodide muscarinic M3 receptor antagonist inhibited DS‑induced pacemaker depolarizations, whereas methoctramine, a muscarinic M2 receptor antagonist, did not. When guanosine 5'‑[β‑thio] diphosphate (GDP‑β‑S; 1 mM) was in the pipette solution, DS marginally induced pacemaker depolarizations, whereas low Na+ solution externally eliminated the generation of pacemaker potentials and inhibited the DS‑induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the DS‑induced pacemaker depolarizations. Pretreatment with Ca2+‑free solution and thapsigargin, a Ca2+‑ATPase inhibitor in the endoplasmic reticulum, also eliminated the generation of pacemaker currents and suppressed the DS‑induced pacemaker depolarizations. In addition, [Ca2+]i analysis revealed that DS increased [Ca2+]i. These results suggested that DS modulates pacemaker potentials through muscarinic M3 receptor activation in ICCs by G protein‑dependent external and internal Ca2+ regulation and external Na+. Therefore, DS were observed to affect intestinal motility through ICCs.

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