CALCIUM AND ION CHANNELS IN SMOOTH MUSCLE

本申请研究的长期目标是了解 离子通道活性与起始和 调节平滑肌收缩。 最重要的活动 这种关系是离子通道活性对 内部Ca 2+，这反过来又影响细胞的收缩状态。 由于平滑肌在如此重要的健康相关疾病中起着关键作用， 控制血压、胃肠蠕动、组织 灌注等，对这种关系的理解将奠定 了解正常和疾病状态的基础，并应 有助于为新的治疗干预指明方向。 具体而言是 建议的研究有三个直接目标：（1）了解作用 牵张激活的阳离子通道在肌源性成分的 通过其对内部Ca 2+的影响，拉伸诱导收缩，（2） 为了了解咖啡因激活的阳离子通道在 调节内部Ca 2+，（3）了解神经元的作用， 递质和细胞内Ca ~（2+）在离子生成和调节中的作用 通道活动潜在的自发瞬时外向电流， 可以反过来影响细胞的收缩状态。 一个共同的主题 在这些研究中， Ca 2+和离子通道活性。 因此，离子通道活性影响 通过允许Ca 2+进入细胞和细胞内， 内部Ca ~（2+）的变化反过来又会影响离子的活性。 渠道 该方法主要涉及膜片钳技术， 记录全细胞和单通道电流， 细胞内Ca 2+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+.