Pilla Arthur, Fitzsimmons Robert, Muehsam David, Wu June, Rohde Christine, Casper Diana
Departments of Biomedical Engineering, Columbia University and Orthopedics, Mount Sinai School of Medicine, New York, NY, United States.
Biochim Biophys Acta. 2011 Dec;1810(12):1236-45. doi: 10.1016/j.bbagen.2011.10.001. Epub 2011 Oct 8.
The transduction mechanism for non-thermal electromagnetic field (EMF) bioeffects has not been fully elucidated. This study proposes that an EMF can act as a first messenger in the calmodulin-dependent signaling pathways that orchestrate the release of cytokines and growth factors in normal cellular responses to physical and/or chemical insults.
Given knowledge of Ca(2+) binding kinetics to calmodulin (CaM), an EMF signal having pulse duration or carrier period shorter than bound Ca(2+) lifetime may be configured to accelerate binding, and be detectable above thermal noise. New EMF signals were configured to modulate calmodulin-dependent signaling and assessed for efficacy in cellular studies.
Configured EMF signals modulated CaM-dependent enzyme kinetics, produced several-fold increases in key second messengers to include nitric oxide and cyclic guanosine monophosphate in chondrocyte and endothelial cultures and cyclic adenosine monophosphate in neuronal cultures. Calmodulin antagonists and downstream blockers annihilated these effects, providing strong support for the proposed mechanism.
Knowledge of the kinetics of Ca(2+) binding to CaM, or for any ion binding specific to any signaling cascade, allows the use of an electrochemical model by which the ability of any EMF signal to modulate CaM-dependent signaling can be assessed a priori or a posteriori. Results are consistent with the proposed mechanism, and strongly support the Ca/CaM/NO pathway as a primary EMF transduction pathway.
The predictions of the proposed model open a host of significant possibilities for configuration of non-thermal EMF signals for clinical and wellness applications that can reach far beyond fracture repair and wound healing.
非热电磁场（EMF）生物效应的转导机制尚未完全阐明。本研究提出，在正常细胞对物理和/或化学损伤的反应中，电磁场可作为钙调蛋白依赖性信号通路中的第一信使，协调细胞因子和生长因子的释放。
鉴于已知钙离子（Ca(2+)）与钙调蛋白（CaM）的结合动力学，可配置脉冲持续时间或载波周期短于结合钙离子寿命的电磁场信号，以加速结合，并在热噪声之上被检测到。新的电磁场信号被配置用于调节钙调蛋白依赖性信号，并在细胞研究中评估其功效。
配置的电磁场信号调节了钙调蛋白依赖性酶动力学，使软骨细胞和内皮细胞培养物中的关键第二信使（包括一氧化氮和环磷酸鸟苷）以及神经元培养物中的环磷酸腺苷增加了几倍。钙调蛋白拮抗剂和下游阻滞剂消除了这些作用，为所提出的机制提供了有力支持。
了解钙离子与钙调蛋白的结合动力学，或任何信号级联特异性的离子结合动力学，允许使用电化学模型，通过该模型可以先验或后验地评估任何电磁场信号调节钙调蛋白依赖性信号的能力。结果与所提出的机制一致，并强烈支持钙/钙调蛋白/一氧化氮途径作为主要的电磁场转导途径。
所提出模型的预测为非热电磁场信号的配置开辟了许多重大可能性，可用于临床和健康应用，其应用范围可能远远超出骨折修复和伤口愈合。
