Komulainen H, Bondy S C
Toxicol Appl Pharmacol. 1987 Mar 30;88(1):77-86. doi: 10.1016/0041-008x(87)90271-7.
Effects of several alkylmetals on free intrasynaptosomal Ca2+ concentration, [Ca2+]i, were studied in vitro using the fluorescent Ca2+ indicator fura-2. Neurotoxic alkylmetals methylmercury (Met-Hg), triethyllead (TEL), triethyltin (TET), and trimethyltin (TMT) (at 2.5-30 microM) increased [Ca2+]i to different degrees. Met-Hg was the most potent, elevating [Ca2+]i 100-800 nM, dose dependently and significantly more than high K+ (150 nM) or veratridine (350 nM). The effect of Met-Hg could not be inhibited with a Ca2+ channel blocker, verapamil, nor with a Na+ channel blocker, tetrodotoxin. Inhibition of the mitochondrial Ca2+ uptake in situ with rotenone + oligomycin decreased the potency of Met-Hg to elevate [Ca2+]i but did not change the resting [Ca2+]i. Met-Hg also slightly decreased synaptosomal ATP. TEL and TET elevated [Ca2+]i by 100-200 nM. The effect of TEL, but not that of TET, could be blocked with verapamil (36%) and veratridine (67%). TEL was less efficient in the presence of ouabain. Neither TEL nor TET had significant mitochondrial effects in situ contributing to [Ca2+]i. TMT increased [Ca2+]i less than TET while dimethyltin and methyltin were inactive. These results indicate that neurotoxic derivatives of alkylmetals studied increase [Ca2+]i. This occurs mainly either by nonspecific increase (Met-Hg, TET) of Ca2+ leakage through the plasma membrane and/or specific interference with the mechanisms regulating Ca2+ fluxes through the plasma membrane (TEL).
利用荧光钙指示剂fura-2在体外研究了几种烷基金属对突触小体内游离钙离子浓度[Ca2+]i的影响。神经毒性烷基金属甲基汞（Met-Hg）、三乙基铅（TEL）、三乙基锡（TET）和三甲基锡（TMT）（浓度为2.5 - 30 microM）不同程度地升高了[Ca2+]i。Met-Hg的作用最强，使[Ca2+]i升高100 - 800 nM，呈剂量依赖性，且显著高于高钾（150 nM）或藜芦碱（350 nM）。Met-Hg的作用不能被钙通道阻滞剂维拉帕米或钠通道阻滞剂河豚毒素抑制。用鱼藤酮 + 寡霉素原位抑制线粒体对钙离子的摄取降低了Met-Hg升高[Ca2+]i的效力，但未改变静息[Ca2+]i。Met-Hg还轻微降低了突触体ATP。TEL和TET使[Ca2+]i升高100 - 200 nM。TEL的作用可被维拉帕米（36%）和藜芦碱（67%）阻断，而TET的作用则不能。在哇巴因存在的情况下，TEL的效力较低。TEL和TET在原位对[Ca2+]i均无显著的线粒体作用。TMT升高[Ca2+]i的幅度小于TET，而二甲基锡和甲基锡则无活性。这些结果表明，所研究的烷基金属神经毒性衍生物会升高[Ca2+]i。这主要是通过质膜非特异性增加Ca2+泄漏（Met-Hg、TET）和/或特异性干扰调节Ca2+通过质膜流动的机制（TEL）来实现的。
