INTRACELLULAR CA2+ CHANNELS OF STRIATED MUSCLE

细胞内钙库的钙通道，如ryanodine和IP 3 受体，最终负责产生Ca 2+信号 在细胞内当表面膜被电压刺激时， 神经递质或激素。 活化动力学和 细胞内Ca 2+通道的失活是导致 普遍存在的细胞内Ca 2+释放机制称为Ca 2+诱导的Ca 2 + release. 该提案的重点是分子和动力学性质的 心肌和骨骼肌的兰尼碱受体和IP 3受体 肌浆网的作用， 肌浆网Ca ~（2+）的变化 刺激-收缩偶联期间的渗透性。 该提案的具体目标是：1）研究阻断或激活 从Buthotus judaicus纯化的肽毒素和 2）确定Ca 2+的大小， Ryanodine控制的池和Ryanodine介导的Ca 2+释放速率， 心肌中的IP 3受体;以及3）确定心肌中的IP 3受体的分子水平。 兰尼碱受体特异性毒素分子克隆 技术. 具体目标是从这方面取得的经验中得出的。 细胞内Ca 2+通道功能重建研究组 和使用45 Ca 2+通量和平面双层的组合的表面起源 录制. 该建议的力量在于解决能力， 这些技术在定量框架内使用。

Ca2+ channels of intracellular Ca2+ stores, such as ryanodine and IP3 receptors, are ultimately responsible for the generation of Ca2+ signals within cells when the surface membrane is stimulated by voltage, neurotransmitters, or hormones. The kinetics of activation and inactivation of intracellular Ca2+ channels is responsible for the ubiquitous intracellular Ca2+ release mechanism known as Ca2+-induced Ca2+ release. The proposal focuses on the molecular and kinetic properties of ryanodine receptors and IP3 receptors of cardiac and skeletal muscle sarcoplasmic reticulum with the interest in understanding the contribution of these channels to the changes in sarcoplasmic reticulum Ca2+ permeability during stimulus-contraction coupling. The specific aims of the proposal are 1) to study the block or activation ryanodine receptors by peptide toxins purified from Buthotus judaicus and Heloderma horridium horridium venoms; 2) to establish the size of the Ca2 pools controlled by, and rates of Ca2+ release mediated by, ryanodine and IP3 receptors in cardiac muscle; and 3) to determine the molecular structure of ryanodine receptor-specific toxins by molecular cloning techniques. The specific aims are drawn from the experience gained by this group on the functional reconstitution of Ca2+ channels of intracellular and surface origin using a combination of 45Ca2+ fluxes and planar bilayer recording. The strength of the proposal resides in the resolving power of these techniques when used within a quantitative framework.