Yim Peter D, Gallos George, Perez-Zoghbi Jose F, Trice Jacquelyn, Zhang Yi, Siviski Matthew, Sonett Joshua, Emala Charles W
Departments of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY USA.
J Smooth Muscle Res. 2013;49:112-24. doi: 10.1540/jsmr.49.112.
Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.
气道平滑肌（ASM）收缩增强是哮喘病理生理学的一个重要组成部分。我们已经表明，配体门控氯离子通道在诱导收缩的维持阶段调节ASM收缩张力，然而，氯离子通量在去极化诱导收缩中的作用仍未完全了解。为了更好地理解这些条件下氯离子通量的作用，我们测量了肌肉力量（人ASM、豚鼠ASM）、外周小气道管腔面积（大鼠ASM）和气道平滑肌质膜电位（人培养ASM）。我们发现，在离体豚鼠气道环、人ASM条带以及大鼠肺切片中的外周小气道中，在用四乙铵氯化物（TEA）阻断钾通道诱导去极化收缩后，尼氟酸可使其松弛。在分离的人气道平滑肌细胞中，通过荧光指示剂或全细胞膜片钳测量发现，TEA可诱导去极化，而尼氟酸可逆转这种去极化。这些发现表明，ASM去极化诱导的收缩依赖于氯离子通道活性。靶向氯离子通道可能是一种使支气管收缩性疾病中过度收缩的气道平滑肌松弛的新方法。
