MODULATION OF IONIC CHANNELS IN CULTURED OSTEOBLASTS

培养成骨细胞中离子通道的调节

• 批准号: 3437687
• 负责人: BRENDAN S WONG
• 金额: $ 9.71万
• 依托单位: BAYLOR COLLEGE OF DENTISTRY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3437687
• 关键词: calcium channel; cell differentiation; cell growth regulation; cell membrane; cytoskeleton; electrophysiology; evoked potentials; hormone regulation /control mechanism; ion transport; laboratory rat; membrane channels; membrane permeability; membrane potentials; microelectrodes; muscle cells; neurons; osteoblasts; parathyroid hormones; potassium channel; vascular smooth muscle; voltage /patch clamp

Bone is a complex living tissue containing osteoblasts and osteoclasts which are primarily responsible for bone formation and resorption. Recently, a number of voltage-gated channels have been found to be present in the cell membranes of osteoblasts. These channels which allow ion movements across the membrane down their electrochemical gradients are traditionally found in excitable membranes such as neurons, various types of muscle cells as well as in secretory cells. Osteoblasts secrete a number of growth factors and thus may have a variety of ionic channels that are also present in other secretory cells. External factors such as hormones, drugs and mechanical forces are known to modulate the physiological functions of bone cells. Parathyroid hormone, for example, is known to first depolarize the membrane of osteoblasts, which is then followed, several minutes later, by membrane hyperpolarization. The mechanism of action of parathyroid hormone in inducing these membrane potential changes remains largely unknown. However, variations in the permeability of ionic channels can easily account for the changes observed. The depolarization caused by the entry of cations into a cell can also trigger the release of second messengers, which in turn, can modulate the properties of ionic channels. Mechanical forces also play an important role in the differentiation and growth of the skeleton, with increased activity resulting in bone growth while a decrease in activity would lead to mineral loss. This would suggest the presence of receptors in bone cells that are sensitive to stretch or tension. Indeed, stretch-activated ionic channels have been found in a variety of cell types. It is the objective of this proposal to utilize varying aspects of the patch-clamp technique, which is uniquely suitable for studying the properties of ionic channels, to determine how these channels are modulated by external factors using cultured osteoblasts dissociated enzymatically from neonatal rat calvaria. The properties of the ionic channels found in these osteoblasts will then be compared to those that have been reported in other traditionally excitable membranes.

骨是含有成骨细胞的复杂活组织， 破骨细胞主要负责骨形成， 再吸收 最近，许多电压门控通道已被发现。 发现存在于成骨细胞的细胞膜中。 这些 通道允许离子穿过膜向下运动， 电化学梯度传统上在可激发的 细胞膜，如神经元，各种类型的肌肉细胞，以及 就像分泌细胞一样。 成骨细胞分泌大量生长因子 因此可能具有多种离子通道， 存在于其他分泌细胞中。 等外部因素 已知激素、药物和机械力调节 骨细胞的生理功能。 甲状旁腺激素， 例如，已知首先去骨细胞膜， 几分钟后， 超极化 甲状旁腺激素的作用机制 在诱导这些膜电位变化的过程中， 未知 然而，离子通道渗透性的变化 可以很容易地解释所观察到的变化。 去极化 由阳离子进入细胞引起的炎症也会触发 第二信使的释放，反过来，可以调节 离子通道的特性。 机械力也起着 在骨骼的分化和生长中起重要作用， 增加的活动导致骨生长， 会导致矿物质流失。 这表明， 骨细胞中存在对拉伸敏感的受体 或者紧张 事实上，拉伸激活离子通道已经被 存在于多种细胞类型中。 这是我们的目标 利用膜片钳技术的不同方面的提议， 这是唯一适合研究离子的性质， 通道，以确定这些通道如何被外部调制 因子使用培养的成骨细胞酶促解离， 新生大鼠颅骨 发现的离子通道的性质 在这些成骨细胞中，然后将与那些已经被 在其他传统的可兴奋膜中也有报道。