氢离子和磷酸肌醇混合物对心肌ATP敏感性钾通道的调节作用  

The Effect of Proton and PPIs on the Regulation of Cardiac ATP Sensitive Potassium Channel

作　　者：陈旭华[1] 黄健[1] Jonathan Makielski 浦介麟[1] 

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外心血管病医院心律失常诊治中心,北京市100037 [2]University of Wisconsin School of Medicine and Public Health

出　　处：《中国分子心脏病学杂志》2015年第4期1384-1389,共6页Molecular Cardiology of China

摘　　要：目的心肌缺血早期,细胞内ATP浓度未明显降低的情况下KATP通道即可开放,机制不明。本实验采用豚鼠和克隆的心肌KATP通道(Kir6.2/SUR2a),探讨细胞内环境因素对KATP通道活性的影响。方法采用inside-out膜片钳记录法,细胞外、内钾离子浓度为4.0/140m M,钳压=0m V。结果在细胞内液PH值由7.25降至6.0后,克隆型KATP通道的电流强度由40.7流强度由胞外降至22.0流强度由胞外;大鼠KATP通道的电流强度由20.2流强度由胞外降至10.6流强度由胞外(P<0.01),单通道电流幅度由2.55p A降至1.97p A,Po从0.84降到0.38。在PH分别为7.25和6.0时,ATP 0.1m M对KATP通道的抑制率分别为48.2制率度)胞和10.8制率度)胞(P<0.05)。磷酸肌醇混合物(PPIs)(0.5mg/ml)使ATP对KATP通道的抑制率降低50%以上,使氢离子对KATP通道电流的抑制率从57%降至20%(P<0.01),PPIs可使开放几率显著增加,但对通道电流幅值影响不明显。结论氢离子通过直接抑制或降低KATP通道对ATP的敏感性对KATP通道起双重调节作用。PPIs降低KATP通道对ATP的敏感性,同时校正氢离子对KATP通道Po的抑制作用,对KATP通道起兴奋作用并部分拮抗氢离子抑制KATP通道的作用。本研究结论可能为缺氧早期时心肌KATP通道开放的调节机制之一。Objective At the early stage of myocardial ischemia, the ATP-sensitive Potassium channels （KATP） open despite the higher intracellular ATP concentration. The mechanism remains unknown. In this experiment, the effect of intracellular environment on the activity of KATP channels was studied by using cloned （Kir6.2/SUR2a） and rat KATP channels. Methods The inside-out patch clamp technique was used, the extra- and intra-cellular Potassium concentration were 4.0/140Mm, clamp voltage was 0mV. Results When the intracellular PH value decreased from 7.25 to 6.0, the current amplitude of cloned KATP channel reduced from 40.7＋4.6pA to 22.0＋4.6pA （P〈0.01） ; similarly, the current amplitude of rat cells reduced from 20.2 ＋ 1.SPA to 10.6 ＋ 0.4pA; the unitary current amplitude fell from 2.55pA to 1.97pA, and Po fell from 0.84 to 0.38. When PH were at 7.25 and 6.0, the inhibition rates of KATP channel at 0.1mM were 48.2 ＋ 7.1% and 10.8 ＋ 4.2% （P〈0.05）, respectively. Phosphoinositols （PPIs） （0.5mg/ml） completely restored rundown KATP channel activity, ATP inhibition rate relatively decreased greater than 50%, and besides, the inhibiting rate of H＋ on KATP channel decreased from 57% to 20% （P 〈 0.01）. The mechanism of PPIs removed the inhibition of H＋ on KATP channel was to restore the inhibition of H＋ on Po, rather than on unitary current amplitude. Conclusions The H＋ regulates KATP channel activity both by direct inhibition and reduction of the sensitivity of KATP to ATP. PPIs not only reduce KATP channel sensitivity to ATP so that activate the channels, but also restore the Po inhibited by H＋, which partially antagonized the inhibition effect of H＋ on KATP channel. Our finding may be one of the mechanisms of the regulation of cardiac KATP channels in hypoxia.

关 键 词：ATP敏感性钾通道 调节 心肌 缺氧 

分 类 号：R542.2[医药卫生—心血管疾病]