Fleischer S, Inui M
Department of Molecular Biology, Vanderbilt University, Nashville, TN 37235.
Prog Clin Biol Res. 1988;273:435-50.
The calcium uptake and release machinery in heart SR have been characterized: (1) The calcium pump membrane is involved in energized Ca2+ uptake enabling muscle to relax. The calcium pump protein (CPP) in heart SR is modulated by protein kinase phosphorylation of phospholamban lowering the KCa2+. We conclude that in the membrane, phospholamban elevates KCa2+ of calcium pump protein. Phosphorylation of phospholamban attenuates the influence of phospholamban. In the limit, the intrinsic KCa2+ of calcium pump protein in heart and skeletal muscle are approximately the same. (2) The junctional face membrane is involved in calcium release which triggers muscle contraction. Ryanodine is a specific modulator of the Ca2+ release channels of SR which are involved in excitation-contraction coupling. The ryanodine receptor has been isolated, found to be equivalent to the feet structures, and on reconstitution into bilayers, identified as the calcium release channel of SR. The calcium release channel of SR is closed by ruthenium red and Mg2+ and opened by Ca2+ and ATP and low ryanodine concentration. The calcium release channel of SR is not effected by drugs such as nitrendipine, diltiazem and D-600 which modulate the slow inward Ca2+ channel of the plasmalemma/transverse tubule. (3) The calcium release channels from heart and skeletal muscle SR are similar but not identical (Table IV). Important differences distinguish the calcium release machinery in heart from that of skeletal muscle. 1. In heart there are two sources of calcium fluxes: a) extracellular Ca2+ enters via the plasmalemma slow inward calcium current; and b) "Ca2+ induced Ca2+ release" from SR. In skeletal muscle, SR is the single main source of calcium which enters via "Depolarization induced calcium release". 2. The calcium release channel from heart SR has a lower Mr approximately 340,000 vs 360,000 for skeletal muscle. 3. Ryanodine binding in cardiac SR is distinct from that in skeletal muscle (Fig. 7). 4. The isolated calcium release channel from heart SR is more sensitive to Ca2+ for calcium release (Hymel et al. 1988c). Significant progress has been achieved in identifying the calcium release channel of SR in heart and skeletal muscle. The focus of excitation-contraction coupling now shifts to defining the precise nature of the coupling of excitation to contraction.
（1）钙泵膜参与了使肌肉能够舒张的能量驱动的Ca2+摄取过程。心脏肌浆网中的钙泵蛋白（CPP）受受磷蛋白的蛋白激酶磷酸化调节，从而降低Ca2+亲和力。我们得出结论，在膜中，受磷蛋白会提高钙泵蛋白的Ca2+亲和力。受磷蛋白的磷酸化会减弱其影响。在极限情况下，心脏和骨骼肌中钙泵蛋白的固有Ca2+亲和力大致相同。（2）连接面膜参与钙释放，从而引发肌肉收缩。雷诺丁是肌浆网Ca2+释放通道的特异性调节剂，这些通道参与兴奋-收缩偶联。雷诺丁受体已被分离出来，发现与足状结构等同，并且在重构到双层膜中时，被鉴定为肌浆网的钙释放通道。肌浆网的钙释放通道可被钌红和Mg2+关闭，并被Ca2+、ATP和低浓度雷诺丁打开。肌浆网的钙释放通道不受诸如尼群地平、地尔硫䓬和D-600等调节质膜/横管慢内向Ca2+通道的药物的影响。（3）心脏和骨骼肌肌浆网的钙释放通道相似但并不相同（表IV）。心脏和骨骼肌的钙释放机制存在重要差异。1. 在心脏中，钙通量有两个来源：a）细胞外Ca2+通过质膜慢内向钙电流进入；b）肌浆网的“Ca2+诱导的Ca2+释放”。在骨骼肌中，肌浆网是钙的单一主要来源，钙通过“去极化诱导的钙释放”进入。2. 心脏肌浆网的钙释放通道分子量较低，约为340,000，而骨骼肌的为360,000。3. 心脏肌浆网中的雷诺丁结合与骨骼肌中的不同（图7）。4. 从心脏肌浆网分离出的钙释放通道对钙释放对Ca2+更敏感（海梅尔等人，1988c）。在鉴定心脏和骨骼肌中肌浆网的钙释放通道方面已取得重大进展。兴奋-收缩偶联的重点现在转向确定兴奋与收缩偶联的精确性质。
