ION CHANNELS OF UTERINE MUSCLE DURING PREGNANCY

早产是由于各种原因造成的，比如多胎妊娠， 感染、羊水过多和子宫异常。然而，通常它的 病因不明(“特发性”)。早产的管理取决于 关于抑制子宫平滑肌收缩的研究。离子通道 (例如，电压依赖的钙通道、各种K通道、拉伸- 子宫肌层细胞膜的激活通道和C_1通道 在兴奋-收缩耦合中起重要作用。离子通道 控制细胞内钙水平，从而控制细胞的收缩状态 子宫肌层细胞。在怀孕期间，这些离子通道被 长期接触各种激素，如雌激素、黄体酮或 HCG。静息膜电位与子宫肌层棘波的形成 怀孕期间的变化。我们将首先调查 大鼠子宫平滑肌细胞离子通道特性的研究 怀孕期间和长期服用雌激素和/或 孕激素。然后我们将检查各种物质的影响 和条件，这被认为与疾病的病因有关 早产(如白三烯、血小板活化因子、缺血、 机械拉伸)，在离子通道上。这些研究将有助于 我们对预防和治疗早产的认识。 此外，它们可能为特发性早产的原因提供线索。 劳力。我们还将研究酵母菌发酵剂对小鼠的影响。 子宫肌层离子通道的活性。在早产儿的管理中 分娩时，β肾上腺素能激动剂(如利托君和特布他林)有 已被广泛用于宫缩治疗。由此带来的增长 在子宫肌层细胞内的cAMP被认为介导了这种抑制 通过减少游离钙的可获得性来减少子宫收缩。 然而，β-激动剂的产酵解作用的机制仍然是 在亚细胞和膜水平上未知。有人建议说， 该cAMP；(A)激活钙泵，(B)抑制肌球蛋白光 (C)抑制钙通道，和/或(D) 增强K通道活性。产酸剂，镁，被认为是 作用于钙离子通道，阻止钙离子进入细胞。其中一些 这些被提出的机制将在我们的电生理学中得到阐明 分离的单个子宫肌层细胞的实验。尽管测试版- 肾上腺素能生育酵解剂是为了β2特异性而选择的，他们确实是这样做的 具有一些β1活性，这会引起心血管方面的问题 效果。因此，我们还将测试测试版的效果- 肾上腺素能代谢剂对心肌的作用，提供全面 关于他们心血管副作用的信息。最后，研究 也将在分离的人类子宫肌层组织上进行研究，以与 在动物组织上的结果，以提供新的信息 更好地管理人类的早产。

Preterm labor occurs due to various causes, such as multiple gestation, infection, polyhydramnios, and uterine anomalies. However, often its etiology is unknown ("idiopathic"). Management of preterm labor depends on inhibition of contraction of uterine smooth muscle. The ion channel (e.g., voltage-dependent Ca2+ channels, various K+ channels, stretch- activated channels, and C1-channels) of myometrial cell membrane play an important role in excitation-contraction coupling. The ion channels control the cytosolic Ca2+ level, and hence the contractile sate of the myometrial cells. During pregnancy, these ion channels are modified by chronic exposure to various hormones, such as estrogen, progesterone or hCG. Resting membrane potential and spike formation of myometrium change during pregnancy. We will first investigate the change in the properties of ion channels of rat uterine smooth muscle cells during pregnancy and during chronic treatment with estrogen and/or progesterone. Then we will examine the effects of various substances and conditions, which are considered to be related to the etiology of preterm labor (e.g., leukotrienes, platelet activating factor, ischemia, mechanical stretch), on the ion channels. These studies will facilitate our understanding of the prevention and treatment of preterm labor. Further, they may provide a clue as to the cause of idiopathic preterm labor. We will also examine the effects of tocolytic agents on the activity of the myometrial ion channels. In management of preterm labor, beta-adrenergic agonists (such as ritodrine and terbutaline) have been widely used for uterine tocolytic therapy. The resulting increase in cAMP within the myometrial cell is believed to mediate the inhibition of uterine contraction, by decreasing the availability of free Ca2+. However, the mechanism of the tocolytic action of beta-agonists is still unknown at the subcellular and membrane level. It has been suggested that cAMP; (a) activates the Ca2+ pump, (b) inhibits the myosin-light chain kinase by phosphorylation, (c) inhibit Ca2+ channels, and/or (d) enhances K+ channel activity. The tocolytic agent, Mg2+,, is thought to act on the Ca2+ channel to prevent Ca2+ entry into the cell. Some of these proposed mechanisms will be clarified in our electrophysiological experiments on isolated single myometrial cells. Although the beta- adrenergic tocolytic agents are selected for beta 2 specificity, they do possess some beta 1 activity, which give rise to cardiovascular side effects. therefore, we will also test the effects of the beta- adrenergic tocolytic agents on cardiac muscle, to provide comprehensive information about their cardiovascular side effects. Finally, studies will also be done on isolated human myometrial tissue, to compare with the results on animal tissue, in order to provide new information for better management of preterm labor in humans.