ION CHANNELS CONTROLLING BONE REMODELING

描述（改编自申请人的摘要）：本发明的目标是： 这个项目的目的是确定离子通道是如何调节成骨细胞功能的。 的 有待检验的假设是离子通道调节成骨细胞功能 从而导致骨骼重塑 的机制 1，25-二羟维生素D3和维生素D3代谢物影响通道活性 并研究骨钙素的释放。 在具体目标#1中，研究将试图确定作用机制 1，25（OH）2D和维生素D3代谢物对电压门控钙通道的影响 在成骨细胞中。 研究人员将确定是否影响 的1，25（OH）2D3需要结合到其胞质受体， 蛋白质合成在这方面涉及。 第二个角色 信使，如钙和蛋白激酶C，在控制的 将探索电压门控钙通道的活性。 此外，委员会认为， 将努力阐明是否有直接激活 通过与通道本身结合或是否介导了这种效应 通过G蛋白。 实验将确定维生素D3 代谢物通过调节钙介导的 事件 在具体目标#2中，申请人将确定钙如何通过 电压依赖性钙通道控制骨钙素释放。 的 将研究钾电导的调制， 钾通道的信号，调节骨钙素释放将是 探讨了 目的是确定ROS细胞中的钾通道是如何 通过影响骨钙素释放的信号，包括钙， cAMP或蛋白激酶C。申请人还将确定维生素 D3、雌二醇、孕酮或糖皮质激素调节钾 电导率 最后，钾对骨钙素释放的调节 将确定去极化。

DESCRIPTION (Adapted from the Applicant's Abstract): The goal of this project is to define how ion channels regulate osteoblast function. The hypothesis to be tested is that ion channels regulate osteoblast function and therefore bone remodeling. The mechanism by which 1,25-dihydroxyvitamin D3 and vitamin D3 metabolites affect channel activity and osteocalcin release will be investigated. In Specific Aim #1, studies will attempt to define the mechanism of action of 1,25(OH)2D and vitamin D3 metabolites on voltage-gated calcium channels in osteoblast cells. The investigator will determine whether the effects of 1,25(OH)2D3 require binding to its cytosolic receptor and whether protein synthesis is involved in this regard. The role of second messengers, such as calcium and protein kinase C, in controlling of the activity of voltage-gated calcium channels will be explored. Furthermore, efforts will be made to elucidate whether there is direct activation of the channel by binding to the channel itself or whether this effect is mediated through G proteins. Experiments will determine whether vitamin D3 metabolites alter osteocalcin release by modulating calcium-mediated events. In Specific Aim #2, the applicant will determine how calcium influx through voltage-dependent calcium channels controls osteocalcin release. The modulation of potassium conductances will be investigated and the control of potassium channels by signals which regulate osteocalcin release will be explored. The intent is to define how potassium channels in ROS cells are modulated by signals which affect osteocalcin release, including calcium, cAMP or protein kinase C. The applicant will also determine whether vitamin D3, estradiol, progesterone, or glucocorticoids modulate potassium conductances. Finally, the regulation of osteocalcin release by potassium depolarization will be determined.