单价和二价离子对Ca(2+)门控的心肌Ca(2+)释放通道（雷诺丁受体）的调节作用

Modulation of Ca(2+)-gated cardiac muscle Ca(2+)-release channel (ryanodine receptor) by mono- and divalent ions.

作者信息

Liu W, Pasek D A, Meissner G

机构信息

Department of Physiology, University of North Carolina, Chapel Hill 27599-7260, USA.

出版信息

Am J Physiol. 1998 Jan;274(1):C120-8. doi: 10.1152/ajpcell.1998.274.1.C120.

DOI:10.1152/ajpcell.1998.274.1.C120

PMID:9458720

Abstract

The effects of mono- and divalent ions on Ca(2+)-gated cardiac muscle Ca(2+)-release channel (ryanodine receptor) activity were examined in [3H]ryanodine-binding measurements. Ca2+ bound with the highest apparent affinity to Ca2+ activation sites in choline chloride medium, followed by KCl, CsCl, NaCl, and LiCl media. The apparent Ca2+ binding affinities of Ca2+ inactivation sites were lower in choline chloride and CsCl media than in LiCl, NaCl, and KCl media. Sr2+ activated the ryanodine receptor with a lower efficacy than Ca2+. Competition studies indicated that Li+, K+, Mg2+, and Ba2+ compete with Ca2+ for Ca2+ activation sites. In 0.125 M KCl medium, the Ca2+ dependence of [3H]ryanodine binding was modified by 5 mM Mg2+ and 5 mM beta,gamma-methyleneadenosine 5'-triphosphate (a nonhydrolyzable ATP analog). The addition of 5 mM glutathione was without appreciable effect. Substitution of Cl- by 2-(N-morpholino)ethanesulfonic acid ion caused an increase in the apparent Ca2+ affinity of the Ca2+ inactivation sites, whereas an increase in KCl concentration had the opposite effect. These results suggest that cardiac muscle ryanodine receptor activity may be regulated by 1) competitive binding of mono- and divalent cations to Ca2+ activation sites, 2) binding of monovalent cations to Ca2+ inactivation sites, and 3) binding of anions to anion regulatory sites.

摘要

在[³H]ryanodine结合测量中检测了单价和二价离子对Ca(2+)门控心肌Ca(2+)释放通道（ryanodine受体）活性的影响。在氯化胆碱培养基中，Ca²⁺与Ca²⁺激活位点结合的表观亲和力最高，其次是氯化钾、氯化铯、氯化钠和氯化锂培养基。在氯化胆碱和氯化铯培养基中，Ca²⁺失活位点的表观Ca²⁺结合亲和力低于氯化锂、氯化钠和氯化钾培养基。Sr²⁺激活ryanodine受体的效能低于Ca²⁺。竞争研究表明，Li⁺、K⁺、Mg²⁺和Ba²⁺与Ca²⁺竞争Ca²⁺激活位点。在0.125M氯化钾培养基中，5mM Mg²⁺和5mM β,γ-亚甲基腺苷5'-三磷酸（一种不可水解的ATP类似物）改变了[³H]ryanodine结合的Ca²⁺依赖性。添加5mM谷胱甘肽没有明显影响。用2-(N-吗啉代)乙磺酸离子取代Cl⁻导致Ca²⁺失活位点的表观Ca²⁺亲和力增加，而氯化钾浓度增加则产生相反的效果。这些结果表明，心肌ryanodine受体活性可能受以下因素调节：1) 单价和二价阳离子与Ca²⁺激活位点的竞争性结合；2) 单价阳离子与Ca²⁺失活位点的结合；3) 阴离子与阴离子调节位点的结合。