Manju L, Nair R Renuka
Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India.
Magnes Res. 2005 Sep;18(3):163-9.
Magnesium has a significant role in the regulation of ion transport. Marginal deficiency of Mg can therefore affect myocardial excitability and contractility. This study was taken up with the objective of examining the inotropic response of the myocardium to variation in extracellular [Mg]o and identifying the ion channels and pumps mediating the inotropic changes. Electrically stimulated rat papillary muscle was used as the experimental model and mechanical changes were recorded using a physiograph. Channel specific antagonists were used to identify the channels mediating the functional changes. Diastolic Ca2+ levels were determined in isolated myocytes by the ratiometric method using the fluorescent indicator Fura2-AM. A negative association was observed between the level of [Mg]o and force of contraction, with a peak at 0.48 mM Mg. The force of contraction in Mg deficient medium (0.48 mM) was 158% of control (1.2 mM Mg) (p < 0.001). Inotropic response to the L-type channel antagonist (verapamil-1 microm) and NaK ATPase inhibitor (Ouabain-0.3 mM) was augmented in Mg deficiency (p < 0.005), indicating activation of the channel and the pump. The response to T-type channel inhibitor (NiCl2-40 microM) was attenuated in Mg deficiency (p < 0.05). The response to the sarcoplasmic reticular Ca pump inhibitor (caffeine-10 mM) and the SR Ca2+ release channel inhibitor (ryanodine-1 microM) were not significantly affected by Mg deficiency. Diastolic level of Ca2+ increased with a decrease in Mg (p < 0.05). The observations of the study lead to the conclusion that the positive inotropic response in Mg deficiency is mediated by an increase in basal Ca2+ combined with Ca-induced-Ca release consequent to Ca2+ influx through L-type Ca channel. Variation in sensitivity to Ca channel blockers and NaK ATPase inhibitor in Mg deficiency can have pharmacological implications.
镁在离子转运调节中发挥着重要作用。因此，镁的轻度缺乏会影响心肌兴奋性和收缩性。本研究旨在检测心肌对细胞外[Mg]o变化的变力反应，并确定介导变力变化的离子通道和泵。以电刺激的大鼠乳头肌作为实验模型，使用生理记录仪记录机械变化。使用通道特异性拮抗剂来确定介导功能变化的通道。通过使用荧光指示剂Fura2-AM的比率法测定分离心肌细胞中的舒张期Ca2+水平。观察到[Mg]o水平与收缩力之间呈负相关，在镁浓度为0.48 mM时达到峰值。缺镁培养基（0.48 mM）中的收缩力是对照组（1.2 mM镁）的158%（p < 0.001）。缺镁时对L型通道拮抗剂（维拉帕米-1微摩尔）和钠钾ATP酶抑制剂（哇巴因-0.3 mM）的变力反应增强（p < 0.005），表明通道和泵被激活。缺镁时对T型通道抑制剂（氯化镍-40微摩尔）的反应减弱（p < 0.05）。缺镁对肌浆网钙泵抑制剂（咖啡因-10 mM）和肌浆网Ca2+释放通道抑制剂（ryanodine-1微摩尔）的反应没有显著影响。Ca2+的舒张期水平随镁的减少而升高（p < 0.05）。该研究的观察结果得出结论，缺镁时的正性变力反应是由基础Ca2+增加以及Ca2+通过L型钙通道内流导致的钙诱导钙释放介导的。缺镁时对钙通道阻滞剂和钠钾ATP酶抑制剂敏感性的变化可能具有药理学意义。
