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心脏线粒体Na+/Ca2+载体上存在Ca2+调节位点的证据。

Evidence for the existence of regulatory sites for Ca2+ on the Na+/Ca2+ carrier of cardiac mitochondria.

作者信息

Hayat L H, Crompton M

出版信息

Biochem J. 1982 Feb 15;202(2):509-18. doi: 10.1042/bj2020509.

Abstract

The Na+-induced efflux of Ca2+ catalysed by the Na+/Ca2+ carrier of cardiac mitochondria is strongly inhibited by extramitochondrial Ca2+. The nature of this inhibition was investigated as follows. (a) The apparent association of external Na+ and the Ca2+ analogue Sr2+ with substrate-binding sites (i.e. those sites involved in cation translocation) is promoted markedly by K+. The inhibition of Na+/Ca2+ exchange by external Ca2+ is affected little by K+. (b) There is a competitive relationship between the binding of external Na+ and external Ca2+ to substrate-binding sites, whereas at low concentrations (less than 4 microM) extramitochondrial Ca2+ is a partial non-competitive inhibitor with respect to external Na+. (c) This inhibiton by external Ca2+ is characterized by a maximal decrease of about 70% in the Vmax of Na+/Ca2+ exchange and by cooperative binding of external Ca2+ to sites that are half saturated by 0.7-0.8 microM free Ca2+. The binding of Ca2+ and Sr2+ to substrate-binding sites shows no co-operativity. These criteria suggest that the Na+/Ca2+ carrier may contain regulatory sites that render the carrier sensitive to changes in extramitochondrial [Ca2+] within the physiological range.

摘要

心脏线粒体的Na⁺/Ca²⁺载体催化的Na⁺诱导的Ca²⁺外流受到线粒体外Ca²⁺的强烈抑制。对这种抑制的性质进行了如下研究。(a) K⁺显著促进外部Na⁺和Ca²⁺类似物Sr²⁺与底物结合位点(即参与阳离子转运的那些位点)的表观结合。外部Ca²⁺对Na⁺/Ca²⁺交换的抑制受K⁺的影响很小。(b) 外部Na⁺和外部Ca²⁺与底物结合位点的结合之间存在竞争关系,而在低浓度(小于4 microM)时,线粒体外Ca²⁺相对于外部Na⁺是部分非竞争性抑制剂。(c) 这种外部Ca²⁺的抑制作用的特征是Na⁺/Ca²⁺交换的Vmax最大降低约70%,以及外部Ca²⁺与游离Ca²⁺浓度为0.7 - 0.8 microM时半饱和的位点协同结合。Ca²⁺和Sr²⁺与底物结合位点的结合没有协同性。这些标准表明,Na⁺/Ca²⁺载体可能含有调节位点,使载体对生理范围内线粒体外[Ca²⁺]的变化敏感。

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Inhibition by Sr2+ of specific mitochondrial Ca2+-efflux pathways.Sr2+对特定线粒体Ca2+外流途径的抑制作用。
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