The possible roles of hyperpolarization-activated cyclic nucleotide channels in regulating pacemaker activity in colonic interstitial cells of Cajal

被引：53

作者：

Shahi, Pawan Kumar ^{[1
]}

Choi, Seok ^{[1
]}

Zuo, Dong Chuan ^{[1
]}

Kim, Man Yoo ^{[2
]}

Park, Chan Guk ^{[2
]}

Kim, Young Dae ^{[2
]}

Lee, Jun ^{[2
]}

Park, Kyu Joo ^{[3
]}

So, Insuk ^{[4
]}

Jun, Jae Yeoul ^{[1
]}

机构：

[1] Chosun Univ, Dept Physiol, Coll Med, Kwangju 501759, South Korea

[2] Chosun Univ, Dept Internal Med, Coll Med, Kwangju 501759, South Korea

[3] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul, South Korea

来源：

JOURNAL OF GASTROENTEROLOGY | 2014年 / 49卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

Hyperpolarization-activated cyclic nucleotide channels; Interstitial cells of Cajal; Pacemaker activity; cAMP; Colon; MOUSE SMALL-INTESTINE; HCN CHANNELS; GASTROINTESTINAL-TRACT; ENDOPLASMIC-RETICULUM; SMOOTH-MUSCLE; EXPRESSION; FREQUENCY; CURRENTS; AMP; RHYTHMICITY;

D O I：

10.1007/s00535-013-0849-3

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Hyperpolarization-activated cyclic nucleotide (HCN) channels are pacemaker channels that regulate heart rate and neuronal rhythm in spontaneously active cardiac and neuronal cells. Interstitial cells of Cajal (ICCs) are also spontaneously active pacemaker cells in the gastrointestinal tract. Here, we investigated the existence of HCN channel and its role on pacemaker activity in colonic ICCs. We performed whole-cell patch clamp, RT-PCR, and Ca2+-imaging in cultured ICCs from mouse mid colon. SQ-22536 and dideoxyadenosine (adenylate cyclase inhibitors) decreased the frequency of pacemaker potentials, whereas both rolipram (cAMP-specific phosphodiesterase inhibitor) and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. CsCl, ZD7288, zatebradine, clonidine (HCN channel blockers), and genistein (a tyrosine kinase inhibitor) suppressed the pacemaker activity. RT-PCR revealed expression of HCN1 and HCN3 channels in c-kit and Ano1 positive colonic ICCs. In recordings of spontaneous intracellular Ca2+ [Ca2+](i) oscillations, rolipram and 8-bromo-cAMP increased [Ca2+](i) oscillations, whereas SQ-22536, CsCl, ZD7288, and genistein decreased [Ca2+](i) oscillations. HCN channels in colonic ICCs are tonically activated by basal cAMP production and participate in regulation of pacemaking activity.

引用

页码：1001 / 1010

页数：10

共 44 条

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