Modulation of Human Cardiac TRPM7 Current by Extracellular Acidic pH Depends upon Extracellular Concentrations of Divalent Cations
Modulation of Human Cardiac TRPM7 Current by Extracellular Acidic pH Depends upon Extracellular Concentrations of Divalent Cations
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DOI：
10.1371/journal.pone.0170923
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发表时间：
2017-01-27
期刊：
影响因子：
3.7
通讯作者：
Mubagwa, Kanigula
中科院分区：
文献类型：
--
作者：
Macianskiene, Regina;Almanaityte, Mante;Mubagwa, Kanigula
TRPM7通道参与多种生理/病理过程。TRPM7电流受质子调节，但已有报道称细胞外pH（pHo）具有相反的作用（增强与抑制）。在人类心肌细胞中，TRPM7的研究少于心脏来源的非心肌细胞。我们在分离的人心房心肌细胞上使用全细胞膜片钳技术来研究酸性pHo对TRPM7电流的影响。在抑制电压依赖性和其他离子通道的情况下，在有或无细胞外二价阳离子存在时，心肌细胞受到细胞外酸化的刺激。在含有Ca2+和Mg2+的细胞外介质中，酸性pHo使TRPM7外向和内向电流增加，但在无细胞外Ca2+和Mg2+时，酸性pHo抑制该电流。在细胞外二价离子存在的情况下，增强作用在pHo低于6时出现，且具有电压依赖性。在无细胞外二价离子时，抑制作用在pHo为6时就已明显，且几乎与电压无关。有冠状动脉疾病病史患者的心肌细胞中TRPM7电流密度较高，与无心肌缺血病史患者的心肌细胞相比，这种差异随酸性pHo增加而增大。我们证明质子诱导的TRPM7电流改变取决于细胞外Ca2+和Mg2+的存在。人类心肌细胞中TRPM7电流密度的变化与临床病史有关，在心房颤动和缺血性心肌病中较高。
TRPM7 channels participate in a variety of physiological/pathological processes. TRPM7 currents are modulated by protons but opposing effects of external pH (pH(o)) (potentiation vs inhibition) have been reported. TRPM7 has been less studied in human cardiomyocytes than in heart-derived non-cardiomyocyte cells. We used the whole-cell patch-clamp technique on isolated human atrial cardiomyocytes to investigate the impact of an acidic pHo on the TRPM7 current. With voltage-dependent and other ion channels inhibited, cardiomyocytes were challenged with external acidification in either the presence or the absence of extracellular divalent cations. TRPM7 outward and inward currents were increased by acidic pHo in extracellular medium containing Ca2+ and Mg2+, but suppressed by acidic pHo in the absence of extracellular Ca2+ and Mg2+. The potentiating effect in the presence of extracellular divalents occurred at pHo below 6 and was voltage-dependent. The inhibitory effect in the absence of extracellular divalents was already marked at pHo of 6 and was practically voltage-independent. TRPM7 current density was higher in cardiomyocytes from patients with history of coronary vascular disease and the difference compared to cardiomyocytes from patients without history of myocardial ischemia increased with acidic pHo. We demonstrate that proton-induced modification of TRPM7 currents depends on the presence of extracellular Ca2+ and Mg2+. Variability of the TRPM7 current density in human cardiomyocytes is related to the clinical history, being higher in atrial fibrillation and in ischemic cardiomyopathy.