Mačianskienė Regina, Almanaitytė Mantė, Jekabsone Aistė, Mubagwa Kanigula
Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania.
PLoS One. 2017 Jan 27;12(1):e0170923. doi: 10.1371/journal.pone.0170923. eCollection 2017.
TRPM7 channels participate in a variety of physiological/pathological processes. TRPM7 currents are modulated by protons but opposing effects of external pH (pHo) (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.
瞬时受体电位阳离子通道M型7（TRPM7）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）存在相反的作用（增强与抑制）。与心脏来源的非心肌细胞相比，TRPM7在人类心肌细胞中的研究较少。我们采用全细胞膜片钳技术，对分离的人类心房肌细胞进行研究，以探讨酸性pHo对TRPM7电流的影响。在电压依赖性和其他离子通道被抑制的情况下，分别在存在或不存在细胞外二价阳离子的条件下，对心肌细胞进行细胞外酸化刺激。在含有Ca2+和Mg2+的细胞外培养基中，酸性pHo可增加TRPM7外向和内向电流，但在不存在细胞外Ca2+和Mg2+时，酸性pHo会抑制TRPM7电流。细胞外二价阳离子存在时的增强作用发生在pHo低于6时，且具有电压依赖性。在不存在细胞外二价阳离子时的抑制作用在pHo为6时就已很明显，且几乎不依赖电压。有冠状动脉疾病史患者的心肌细胞中TRPM7电流密度更高，与无心肌缺血病史患者的心肌细胞相比，随着酸性pHo的增加，这种差异增大。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电流密度的变异性与临床病史有关，在心房颤动和缺血性心肌病中更高。
