MODULATION OF IONIC CHANNELS IN CULTURED OSTEOBLASTS

骨是一种复杂的活组织，含有成骨细胞和 破骨细胞，主要负责骨形成和 再吸收。最近，一些电压门控通道被 发现存在于成骨细胞的细胞膜中。这些 允许离子穿过膜向下移动的通道 传统上，电化学梯度存在于可激发的 膜，如神经元，以及各种类型的肌肉细胞 就像在分泌细胞中。成骨细胞分泌大量的生长 因此可能具有多种离子通道，这些离子通道也 存在于其他分泌细胞中。外部因素，如 已知荷尔蒙、药物和机械力可以调节 骨细胞的生理功能。甲状旁腺激素，用于 例如，已知的是首先使成骨细胞膜去极化， 然后，几分钟后，就是膜 超极化。甲状旁腺激素的作用机制 在诱导这些膜电位变化时，很大程度上 未知。然而，离子通道通透性的变化 可以很容易地解释观察到的变化。去极化 由阳离子进入细胞引起的也可以触发 第二信使的释放，这反过来可以调节 离子通道的特性。机械力也起到了 在骨骼的分化和生长中起着重要的作用， 随着活动的增加导致骨骼生长，而减少 活动不足会导致矿物质流失。这将表明 骨细胞中对拉伸敏感的受体的存在 或者是紧张。事实上，拉伸激活的离子通道已经 发现于各种类型的细胞中。这就是我们的目标 建议利用膜片钳技术的不同方面， 它特别适合于研究离子的性质。 通道，以确定外部设备如何调制这些通道 利用培养的成骨细胞酶解分离的因子 新生大鼠颅骨。已发现的离子通道的性质 然后将这些成骨细胞与那些 在其他传统上可兴奋的膜上也有报道。

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.