Györke Sandor, Györke Inna, Lukyanenko Valeriy, Terentyev Dmitriy, Viatchenko-Karpinski Serge, Wiesner Theodore F
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6551, USA.
Front Biosci. 2002 Jun 1;7:d1454-63. doi: 10.2741/A852.
The amount of Ca2+ released from the sarcoplasmic reticulum (SR) is a principal determinant of cardiac contractility. Normally, the SR Ca2+ stores are mobilized through the mechanism of Ca2+-induced Ca2+ release (CICR). In this process, Ca2+ enters the cell through plasmalemmal voltage-dependent Ca2+ channels to activate the Ca2+ release channels in the SR membrane. Consequently, the control of Ca2+ release by cytosolic Ca2+ has traditionally been the main focus of cardiac excitation-contraction (EC) coupling research. Evidence obtained recently suggests that SR Ca release is controlled not only by cytosolic Ca2+, but also by Ca2+ in the lumen of the SR. The presence of a luminal Ca2+ sensor regulating release of SR luminal Ca2+ potentially has profound implications for our understanding of EC coupling and intracellular Ca2+ cycling. Here we review evidence, obtained using in situ and in vitro approaches, in support of such a luminal Ca2+ sensor in cardiac muscle. We also discuss the role of control of Ca2+ release channels by luminal Ca2+ in termination and stabilization of CICR, as well as in shaping the response of cardiac myocytes to various inotropic influences and diseased states such as Ca2+ overload and heart failure.
肌浆网（SR）释放的Ca2+量是心脏收缩力的主要决定因素。正常情况下，SR的Ca2+储存通过Ca2+诱导的Ca2+释放（CICR）机制进行动员。在此过程中，Ca2+通过质膜电压依赖性Ca2+通道进入细胞，以激活SR膜中的Ca2+释放通道。因此，传统上，胞质Ca2+对Ca2+释放的控制一直是心脏兴奋-收缩（EC）偶联研究的主要焦点。最近获得的证据表明，SR Ca2+释放不仅受胞质Ca2+控制，还受SR腔内Ca2+控制。存在一种调节SR腔内Ca2+释放的腔内Ca2+传感器，这可能对我们理解EC偶联和细胞内Ca2+循环具有深远意义。在这里，我们综述了使用原位和体外方法获得的证据，以支持心肌中存在这种腔内Ca2+传感器。我们还讨论了腔内Ca2+对Ca2+释放通道的控制在CICR终止和稳定中的作用，以及在塑造心肌细胞对各种变力影响和疾病状态（如Ca2+过载和心力衰竭）的反应中的作用。
