Modulation of intracellular Ca2+ levels in the heart by sorcin and FKBP12, two accessory proteins of ryanodine receptors

Modulation of intracellular Ca2+ levels in the heart by sorcin and FKBP12, two accessory proteins of ryanodine receptors
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DOI:
10.1016/s0165-6147(98)01269-3
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发表时间:
1998-12-01
影响因子:
13.8
通讯作者:
Valdivia, HH
Valdivia, HH
中科院分区:
医学1区
文献类型:
--
作者:
Valdivia, HH

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目前的AWARENESS (sorcin-Ca2 +复合物的表观Kd为~ 1 μM) 14,其对心脏ryanodine受体的抑制作用发生在Ca2+浓度范围(0.1-100 μM) 9。因此,这些Ca2+结合域的功能作用必须存在于ryanodine受体作用之后或之前的步骤中。由于Ca2+诱导sorcin从可溶性位置转移到膜细胞位置,因此Ca2+结合域的一个潜在作用是协调sorcin附着于膜或ryanodine受体所需的构象变化。事实上,从pCa 8到pCa 6 Ca2+浓度的增加降低了sorcin14的固有荧光,表明Ca2+依赖的构象变化。
Current AWARENESS (apparent Kd for the sorcin–Ca2+ complex~ 1 μM) 14, its inhibitory effect on cardiac ryanodine receptors occurs over a wide range of Ca2+ concentrations (0.1–100 μM) 9. Hence, the functional role of these Ca2+-binding domains must reside in a step subsequent to, or preceding, the ryanodine receptor effect. Since Ca2+ induces the translocation of sorcin from soluble to membrane cellular locations14, a potential role for the Ca2+-binding domains is to orchestrate the conformational changes required for sorcin attachment to membranes, or to the ryanodine receptor. Indeed, an increase of Ca2+ concentration from pCa 8 to pCa 6 decreases the intrinsic fluorescence of sorcin14, indicative of a Ca2+-dependent conformational change.