Bittar E E, Huang Y P
Department of Physiology, University of Wisconsin, Madison 53706.
Toxicol Appl Pharmacol. 1990 Oct;106(1):71-9. doi: 10.1016/0041-008x(90)90107-6.
Recent work with single muscle fibers from the barnacle Balanus nubilus has shown that the injection of Al into these fibers leads to inhibition of the resting Na efflux and that this involves both the ouabain-sensitive and the ouabain-insensitive components of the efflux. This work also showed that the injection of Al into ouabain-poisoned fibers often leads to a rise in the remaining Na efflux. This observation suggested the possibility that Al is able to stimulate the ouabain-insensitive Na by increasing myoplasmic free Ca2+ and that trigger Ca2+ reaches the myoplasm via voltage-dependent Ca2+ channels. The results obtained are as follows: (i) The injection of AlCl3 into fibers poisoned with ouabain produces a biphasic or monophasic effect on the remaining Na efflux. That is, stimulation is followed by inhibition, or there is only stimulation. (ii) This response is dose-dependent and is seen to take place following the injection of Al in a concentration as low as 0.01 M. (iii) Both Ga3+ and Sc3+ are able to mimic the effect of Al. (iv) Injection of EGTA following peak stimulation of the ouabain-insensitive Na efflux by injected AlCl3 leads to reversal of this response. If, however, EGTA is injected long after the onset of peak stimulation and after ouabain reaches its maximum effect, it is found to be ineffective. (v) The magnitude of the stimulatory response of the ouabain-insensitive Na efflux is a sigmoidal function of external Ca2+ and is almost completely abolished by verapamil, devapamil, and Cd2+ but is unaffected by injecting Mg2+ before or after AlCl3. (vi) Whereas preinjection of Al reduces the response to ryanodine, external preapplication of ryanodine fails to alter the response to Al. The preinjection of deferoxamine (a potent chelator of Al) fails to stop the stimulatory response to Al injection from occurring. Taken together, these findings support the hypothesis that the stimulatory response elicited by Al injection is due to a fall in myoplasmic pCa resulting from activation of voltage-dependent Ca2+ channels and that it involves the operation of the Na+-Ca2+ exchanger in the reverse mode.
近期对藤壶巴氏藤壶单根肌纤维的研究表明，向这些纤维中注入铝会导致静息钠外流受到抑制，且这涉及到钠外流中对哇巴因敏感和不敏感的成分。这项研究还表明，向用哇巴因中毒的纤维中注入铝通常会导致剩余钠外流增加。这一观察结果提示了一种可能性，即铝能够通过增加肌浆游离钙来刺激对哇巴因不敏感的钠外流，并且触发钙通过电压依赖性钙通道进入肌浆。得到的结果如下：（i）向用哇巴因中毒的纤维中注入氯化铝会对剩余钠外流产生双相或单相效应。也就是说，先是刺激，随后是抑制，或者仅有刺激。（ii）这种反应是剂量依赖性的，在注入低至0.01 M浓度的铝后即可观察到。（iii）镓离子和钪离子都能够模拟铝的作用。（iv）在注入氯化铝对哇巴因不敏感的钠外流产生峰值刺激后注入乙二醇双四乙酸（EGTA）会导致这种反应逆转。然而，如果在峰值刺激开始很久之后且哇巴因达到最大效应之后注入EGTA，则发现其无效。（v）对哇巴因不敏感的钠外流的刺激反应幅度是细胞外钙的S形函数，并且几乎完全被维拉帕米、地伐帕米和镉离子消除，但在注入氯化铝之前或之后注入镁离子对其没有影响。（vi）虽然预先注入铝会降低对兰尼碱的反应，但在细胞外预先应用兰尼碱并不能改变对铝的反应。预先注入去铁胺（一种有效的铝螯合剂）并不能阻止对铝注入的刺激反应发生。综上所述，这些发现支持了这样一种假说，即铝注入引发的刺激反应是由于电压依赖性钙通道激活导致肌浆pCa下降，并且它涉及钠钙交换体以反向模式运作。
