CALCIUM AND ION CHANNELS IN SMOOTH MUSCLE

本应用程序中研究的长期目标是理解 离子通道活性与起始性和致密性的关系 对平滑肌收缩的调节。在这件事的中心 相互关系是离子通道活动对血浆中 细胞内的钙离子反过来影响细胞的收缩状态。 由于平滑肌在如此重要的健康相关方面发挥着关键作用 血压、胃肠动力、组织等方面的控制 等，对这种关系的理解将为 了解正常和疾病状态的基础和应该 帮助为新的治疗干预指明方向。具体地说， 拟议的研究有三个直接目标：(1)了解 牵张激活的阳离子通道在肌源性成分中的表达 牵张引起的收缩通过其对内钙的影响，(2) 为了解咖啡因激活的阳离子通道在 以及(3)了解神经细胞内钙离子的作用。 离子产生和调节中的递质和内钙离子 自发性瞬时外向电流背后的通道活动 进而影响细胞的收缩状态。一个共同的主题 纵观这些研究，细胞内的双重关系 钙离子和离子通道活性。因此，离子通道的活动会影响 细胞内钙离子浓度和细胞内钙离子浓度 体内钙离子的变化可以反过来影响离子的活性。 频道。该方法学主要涉及膜片钳技术 记录全电池和单通道电流经常与 细胞内钙离子的同步数字成像显微镜。

The long-term goal of the studies in this application is to understand the relationship between ion channel activity and the initiation and regulation of smooth muscle contraction. At the center of this relationship is the effect of ion channel activity on the levels of internal Ca2+ which, in turn, affects the contractile state of the cell. Since smooth muscle plays a key role in such important health related areas as the control of blood pressure, gastrointestinal motility, tissue perfusion, etc., an understanding of this relationship will lay the groundwork for understanding the normal and diseases states and should help point the way to new therapeutic interventions. Specifically, the proposed studies have three immediate goals: (1) to understand the role of stretch-activated cation channels in the myogenic component of stretch-induced contraction through their effect on internal Ca2+, (2) to understand the role of cation channels activated by caffeine in the regulation of internal Ca2+, and (3) to understand the role of neuro- transmitters and internal Ca2+ in the generation and regulation of ion channel activity underlying spontaneous transient outward currents which can, in turn, affect the contractile state of the cell. A common theme throughout these studies is the dual relationship between intracellular Ca2+ and ion channel activity. Thus, ion channel activity affects the internal Ca2+ concentration by admitting Ca2+ into the cell and the change in internal Ca2+ can, in turn, affect the activity of ion channels. The methodology mostly involves patch-clamp techniques for recording whole-cell and single channel currents often coupled with simultaneous digital imaging microscopy of intracellular Ca2+.