Rosemblit N, Moschella M C, Ondriašová E, Gutstein D E, Ondriaš K, Marks A R
Molecular Cardiology Program, Divisions of Circulatory Physiology and Cardiology, Department of Medicine, New York, New York, 10032, USA.
Dev Biol. 1999 Feb 15;206(2):163-77. doi: 10.1006/dbio.1998.9120.
The release of intracellular calcium (Ca2+) via either inositol 1,4, 5-trisphosphate receptors (IP3R) or ryanodine receptors (RyR) activates a wide variety of signaling pathways in virtually every type of cell. In the present study we demonstrate that at early stages of development IP3R mRNA and functional IP3-gated Ca2+ release channels are widely expressed in virtually all tissues in murine embryos. As organogenesis proceeds, more specialized RyR channels are expressed in many cell types and the triggering mechanisms for intracellular Ca2+ release become more diverse to include IP3-dependent and voltage-dependent and Ca2+-induced Ca2+ release. As development proceeds virtually all cell types continue to express IP3R channels but in excitable cells including skeletal and cardiac muscles the major Ca2+ release channels are RyRs. This developmental switch from predominantly IP3-mediated to both IP3-mediated and IP3-independent pathways for intracellular Ca2+ release is consistent with data showing that IP3R plays an important regulatory role in cellular proliferation and apoptosis, whereas RyR is required for other cellular functions including muscle contraction.
通过肌醇1,4,5 - 三磷酸受体（IP3R）或兰尼碱受体（RyR）释放细胞内钙（Ca2+），几乎能激活每一种类型细胞中的多种信号通路。在本研究中，我们证明在发育早期，IP3R mRNA和功能性IP3门控Ca2+释放通道在小鼠胚胎的几乎所有组织中广泛表达。随着器官发生的进行，更多特异性的RyR通道在许多细胞类型中表达，细胞内Ca2+释放的触发机制变得更加多样，包括IP3依赖性、电压依赖性和Ca2+诱导的Ca2+释放。随着发育的进行，几乎所有细胞类型都继续表达IP3R通道，但在包括骨骼肌和心肌在内的可兴奋细胞中，主要的Ca2+释放通道是RyR。这种从主要由IP3介导的细胞内Ca2+释放途径向IP3介导和IP3非依赖性途径的发育转变，与以下数据一致：IP3R在细胞增殖和凋亡中起重要调节作用，而RyR是包括肌肉收缩在内的其他细胞功能所必需的。
