Dortch-Carnes J, Van Scott M R, Fedan J S
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
J Pharmacol Exp Ther. 1999 May;289(2):911-7.
The relationship between epithelial bioelectric events and epithelium-dependent relaxant and contractile responses of airway smooth muscle in response to hyperosmolar and hypo-osmolar solutions was investigated in guinea pig isolated trachea. Tracheae were perfused with normal or nonisosmotic modified Krebs-Henseleit solution while simultaneously monitoring transepithelial potential difference (VT) and contractile and relaxant responses of the muscle. Baseline VT was -10.1 to -13.3 mV (distal and proximal ends, respectively). Intraluminal amiloride (10(-4) M) induced a 3.7-mV depolarization, verifying that the VT was of epithelial origin. Extraluminal methacholine (3 x 10(-7) M; EC50) caused hyperpolarization and smooth muscle contraction; intraluminal methacholine had very little effect. Increasing intraluminal bath osmolarity via addition of 240 mOsM NaCl or KCl caused an immediate and prolonged depolarization and epithelium-dependent relaxation. Increasing intraluminal bath osmolarity with sucrose evoked similar responses, except that an immediate, transient hyperpolarization and contraction preceded the depolarization and relaxation. Increasing extraluminal bath osmolarity with 240 mOsM NaCl induced depolarization and a longer lasting epithelium-dependent relaxation, whereas extraluminally added 240 mOsM KCl induced a complex smooth muscle response (i.e., transient relaxation followed by contraction), which was accompanied by prolonged depolarization. Intraluminal hypo-osmolarity produced a transient hyperpolarization followed by depolarization along with contraction of the smooth muscle. Bioelectric responses always preceded smooth muscle responses. These results suggest that bioelectric events in the epithelium triggered by nonisosmotic solutions are associated with epithelium-dependent responses in tracheal smooth muscle.
在豚鼠离体气管中，研究了上皮生物电事件与气道平滑肌对高渗和低渗溶液的上皮依赖性舒张和收缩反应之间的关系。用正常或非等渗的改良克雷布斯 - 亨泽莱特溶液灌注气管，同时监测跨上皮电位差（VT）以及肌肉的收缩和舒张反应。基线VT分别为 -10.1至 -13.3 mV（远端和近端）。腔内应用氨氯吡咪（10⁻⁴ M）引起3.7 mV的去极化，证实VT起源于上皮。腔外应用乙酰甲胆碱（3×10⁻⁷ M；EC50）导致超极化和平滑肌收缩；腔内应用乙酰甲胆碱的作用很小。通过添加240 mOsM NaCl或KCl增加腔内浴渗透压会引起立即且持久的去极化和上皮依赖性舒张。用蔗糖增加腔内浴渗透压会引起类似反应，只是在去极化和舒张之前会有立即的、短暂的超极化和收缩。用240 mOsM NaCl增加腔外浴渗透压会引起去极化和持续时间更长的上皮依赖性舒张，而腔外添加240 mOsM KCl会引起复杂的平滑肌反应（即短暂舒张后收缩），并伴有持久的去极化。腔内低渗透压会产生短暂的超极化，随后是去极化以及平滑肌收缩。生物电反应总是先于平滑肌反应。这些结果表明，非等渗溶液触发的上皮生物电事件与气管平滑肌的上皮依赖性反应相关。
