Prasad A M, Inesi G
California Pacific Medical Center, Research Institute, San Francisco, CA, USA.
Minerva Cardioangiol. 2010 Apr;58(2):193-204.
Calcium (Ca2+) signaling plays an essential role in several functions of cardiac myocytes. Transient rises and reductions of cytosolic Ca2+, permitted by the sarcoplasmic reticulum Ca2+ ATPase and other proteins, control each cycle of contraction and relaxation. Prolonged rises of cytosolic Ca2+ are involved in transcriptional activation, including the hypertrophy program. Furthermore, activation of transcriptional pathways produced by excitation of membrane receptors and involving Protein Kinases C and D, calcineurin, mitogen-activated protein kinases and glycogen synthase kinase 3b, generate competitive recruitment of transcriptional factors whereby Ca2+ signaling proteins are downregulated in cardiac hypertrophy. This imbalance leads to defects of muscle contraction (i.e., systole) and relaxation (i.e., diastole), and ultimately cardiac failure. Extensive experimentation on gene transfer and gene deletion is under way to clarify the role of Ca2+ signaling proteins in cardiac hypertrophy and failure, and to evaluate the possibility of gene therapy. On the other hand, the need for pharmacological agents directed to function or transcription/expression of Ca2+ signaling proteins is emphasized, considering their easier delivery and wide population targeting.
钙（Ca2+）信号在心肌细胞的多种功能中起着至关重要的作用。肌浆网Ca2+ ATP酶和其他蛋白质使得胞质Ca2+短暂升高和降低，从而控制着收缩和舒张的每个周期。胞质Ca2+的持续升高参与转录激活，包括肥大程序。此外，由膜受体兴奋产生的、涉及蛋白激酶C和D、钙调神经磷酸酶、丝裂原活化蛋白激酶和糖原合酶激酶3b的转录途径的激活，会竞争性地募集转录因子，从而使Ca2+信号蛋白在心肌肥大中下调。这种失衡会导致肌肉收缩（即收缩期）和舒张（即舒张期）缺陷，最终导致心力衰竭。目前正在进行大量关于基因转移和基因缺失的实验，以阐明Ca2+信号蛋白在心肌肥大和心力衰竭中的作用，并评估基因治疗的可能性。另一方面，考虑到药物更容易给药且能广泛针对人群，人们强调需要针对Ca2+信号蛋白功能或转录/表达的药物。
