Meshul C K, Kriho V, Kriho N, Hopkins W F, Matsumura F, Pappas G D
Veterans Administration Medical Center, Neurocytology Lab, Portland, OR 97201.
Muscle Nerve. 1990 Apr;13(4):348-54. doi: 10.1002/mus.880130411.
Alpha-actinin is a muscle protein located along the Z-disc. Incubation of frog muscle with the calcium ionophore, A23187, can decrease the immunogold labelling of alpha-actinin. Pyridostigmine (PYR) is an inhibitor of acetylcholinesterase, which causes disruption of Z-discs only in the region of the motor endplate. This is probably due to excess influx of calcium ions, leading to activation of proteases. Pretreating animals with the calcium channel blocker diltiazem can significantly reduce damage to the Z-discs at the motor endplate caused by PYR. It was of interest to determine whether the distribution of alpha-actinin had been altered following PYR administration and whether diltiazem could prevent those changes. There was less alpha-actinin labelling at the motor endplate compared to away from this region for all treatment groups. Animals administered diltiazem showed less labelling compared to PYR, but with no disruption of Z-discs at the motor endplate following diltiazem. Pretreatment with diltiazem reduced the incidence of Z-disc damage, but the degree of alpha-actinin labeling at the endplate was less than that seen with diltiazem alone. The greater effect seen at the endplate implies that neuromuscular activity is an important factor. The drugs may be causing a reduction in alpha-actinin labelling by different mechanisms.
α-辅肌动蛋白是一种位于Z盘的肌肉蛋白。用钙离子载体A23187孵育青蛙肌肉会降低α-辅肌动蛋白的免疫金标记。吡啶斯的明（PYR）是一种乙酰胆碱酯酶抑制剂，它仅在运动终板区域导致Z盘破坏。这可能是由于钙离子过度内流，导致蛋白酶激活。用钙通道阻滞剂地尔硫卓预处理动物可显著减少PYR对运动终板Z盘的损伤。确定给予PYR后α-辅肌动蛋白的分布是否发生改变以及地尔硫卓是否能预防这些变化很有意义。与所有治疗组远离该区域相比，运动终板处的α-辅肌动蛋白标记较少。与PYR相比，给予地尔硫卓的动物标记较少，但地尔硫卓给药后运动终板处的Z盘没有破坏。用地尔硫卓预处理可降低Z盘损伤的发生率，但终板处α-辅肌动蛋白标记的程度低于单独使用地尔硫卓时。在终板处观察到的更大影响意味着神经肌肉活动是一个重要因素。这些药物可能通过不同机制导致α-辅肌动蛋白标记减少。
