Faddis M N, Brown J E
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110.
J Gen Physiol. 1993 Jun;101(6):909-31. doi: 10.1085/jgp.101.6.909.
Heparin is thought to inhibit InsP3 binding to receptors involved in the intracellular release of Ca2+. Injection of heparin into Limulus ventral photoreceptors to high intracellular concentrations reduces the amplitude and slows the rate of rise of voltage-clamp currents induced by brief flashes, tends to make the responses to long flashes more "square," and tends to block the light-induced rise in [Ca2+]i detected by arsenazo III. In these ways, intracellular heparin mimics the effects of high concentrations of intracellular BAPTA or EGTA. In addition, the effects of heparin are attenuated by prior injection of BAPTA to high intracellular concentrations. Neomycin and spermine are thought to inhibit phospholipase C activity. Injections of spermine or neomycin to low intracellular concentrations largely mimic the effects of intracellular heparin. These findings suggest that the predominant effect of polyamines is to inhibit light-induced production of InsP3 by phospholipase C activity and thereby reduce the light-induced increase in [Ca2+]i. Our findings suggest that excitation can proceed in the absence of InsP3-induced increases in [Ca2+]i, but (a) the gain and speed of transduction are reduced and (b) adaptation is largely blocked.
肝素被认为可抑制肌醇三磷酸(InsP3)与参与细胞内钙离子(Ca2+)释放的受体结合。向鲎腹侧光感受器内注射高浓度的肝素,可降低短暂闪光诱导的电压钳电流的幅度并减缓其上升速率,使对长时间闪光的反应更趋于“方形”,并倾向于阻断偶氮胂III检测到的光诱导细胞内钙离子浓度([Ca2+]i)升高。通过这些方式,细胞内肝素模拟了高浓度细胞内1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸(BAPTA)或乙二醇双四乙酸(EGTA)的作用。此外,预先向细胞内注射高浓度的BAPTA可减弱肝素的作用。新霉素和精胺被认为可抑制磷脂酶C的活性。向细胞内注射低浓度的精胺或新霉素在很大程度上模拟了细胞内肝素的作用。这些发现表明,多胺的主要作用是通过抑制磷脂酶C的活性来抑制光诱导的InsP3生成,从而减少光诱导的[Ca2+]i升高。我们的发现表明,在没有InsP3诱导的[Ca2+]i升高的情况下兴奋仍可进行,但(a)转导的增益和速度降低,且(b)适应作用在很大程度上被阻断。