Molecular mechanisms underlying the generation of spatiotemporal patterns of cytoplasmic calcium

肌醇1,4,5-三磷酸（IP_3）是磷脂酰肌醇对激素、神经递质和生长因子的信号级联反应产生的第二信使，通过与IP_3受体（IP_3R）结合，导致细胞内Ca^<2+>释放，这是一个IP_3门控的细胞内Ca^<2+>释放通道。Ca^<2+>在细胞质中的释放具有复杂的时空模式，如Ca^<2+>波和Ca^<2+>振荡，并调节多种细胞反应，包括受精、肌肉收缩、分泌、细胞生长、分化、凋亡和突触可塑性。在本研究中，我们从小鼠肺中分离编码2型和3型IP_3R的cdna，发现每种受体与IP_3的结合具有不同的亲和力和协同性。我们还发现，Ca^<2+>离子载体的ATP刺激可诱导COS-7细胞中表达的所有三种类型的小鼠IP_3R簇形成，并且刺激诱导的三种类型的IP_3R簇的大小和形状不同。三种IP_3R类型对IP_3的响应性和胞内分布的多样性可能导致细胞质Ca^<2+>的复杂时空格局的产生。

Inositol 1,4,5-trisphosphate (IP_3) is a second messenger generated by the phosphatidylinositol signaling cascade response to hormones, neurotransmitters, and growth factors and causes Ca^<2+> release from intracellular stores by binding to the IP_3 receptor (IP_3R), which is an IP_3-gated intracellular Ca^<2+> release channel. Ca^<2+> release in the cytoplasm occurs in complex spatial and temporal patterns, such as Ca^<2+> waves and Ca^<2+> oscillations, and regulates many cellular responses, including fertilization, muscle contraction, secretion, cell growth, differentiation, apoptosis, and synaptic plasticity. In this research, we isolated cDNAs encoding type 2 and type 3 IP_3R from mouse lung and found that each type of receptor binds IP_3 with different affinity and cooperativity. We also found that stimulation with ATP of Ca^<2+> ionophore induced cluster formation of all three types of mouse IP_3R expressed in COS-7 cells and that the size and shape of stimulus-induced clusters differ among the three types of IP_3R. The diversity of responsiveness to IP_3 and the intracellular distribution observed among the three IP_3R types may contribute to the generation of the complex spatiotemporal patterns of cytoplasmic Ca^<2+>.