Ryanodine受体结构和药理学性质

Structure and Pharmacology of Ryanodine Receptors

Ｒｙａｎｏｄｉｎｅ受体（ＲｙＲ）是存在于细胞内钙库膜上的一种钙释放通道。在哺乳类动物中，ＲｙＲ存在三种亚型，即骨骼肌型（ＲｙＲ１）、心肌型（ＲｙＲ２）和脑型（ＲｙＲ３），它们分别由ｒｙｒ１、ｒｙｒ２和ｒｙｒ３基因编码。非哺乳类脊椎动物的ＲｙＲ有另外三种亚型，即同时存在于骨骼肌中的αＲｙＲ和βＲｙＲ，以及存在于心肌中的另一亚型。前两者在氨基酸序列上分别与ＲｙＲ１和ＲｙＲ３有较高的同源性。哺乳类和非哺乳类脊椎动物的许多细胞同时表达其中三类或两类ＲｙＲ亚型。本综述介绍ＲｙＲ各类亚型的分子结构及其药理学性质。

Ryanodine receptors (RyR) exist at the membrane of the intracellular calcium stores and function as the calcium release channels in the vertebrate animal cells. In the mammalian animals three isoforms of RyR, skeletal type (RyR1), cardiac type (RyR2) and brain type (RyR3), have been identified, and they are encoded by three distinct genes, ryr1, ryr2 and ryr3, respectively. Meanwhile, in the non mammalian vertebrate animals other three isoforms of RyR have been found: αRyR and βRyR present in the skeletal muscle simultaneously, whose amino acid sequences exhibit the high identity to that of the mammalian RyR1 and RyR3 respectively, and another distinct isoform of RyR in the avian heart. In addition, a large variety of cells of both mammalian and non mammalian vertebrate animal expresses all or two of the three isoforms of RyR simultaneously. Molecular structure and pharmacology of these isoforms of RyR are reviewed in this article.