Sakuma T, Takahashi K, Ohya N, Nakada T, Matthay M A
Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan.
Pharmacol Toxicol. 1998 Jul;83(1):16-22. doi: 10.1111/j.1600-0773.1998.tb01436.x.
Since the effect of an ATP-sensitive potassium channel (KATP channel) opener on the function of alveolar epithelial cells is unknown, the effect of YM934, a newly synthesized KATP channel opener, on potassium influx into the alveolar spaces and alveolar fluid clearance was determined in the resected human lung. An isosmolar albumin solution with a low potassium concentration was instilled into the distal airspaces of resected human lungs. Alveolar fluid clearance was measured by the progressive increase in alveolar protein concentration. Net potassium transport was measured by the change in potassium concentration and alveolar fluid volume. YM934 (10(-4) M) increased net influx of potassium by 140% into the alveolar spaces and also increased alveolar fluid clearance by 60% in the experiments with a potassium concentration of 0.3 mEq/1. Glibenclamide (10(-4) M), a KATP channel blocker, inhibited the YM934-increased influx of potassium transport and the increase in alveolar fluid clearance. Also amiloride (10(-5) M), an inhibitors of apical sodium uptake, blocked the YM934 stimulated increase in net alveolar fluid clearance. These results indicate that a KATP channel opener can effect potassium transport and net vectorial fluid movement across the human alveolar epithelium.
由于ATP敏感性钾通道(KATP通道)开放剂对肺泡上皮细胞功能的影响尚不清楚,因此我们在离体人肺中测定了新合成的KATP通道开放剂YM934对钾流入肺泡腔及肺泡液体清除率的影响。将低钾浓度的等渗白蛋白溶液注入离体人肺的远端气腔。通过肺泡蛋白浓度的逐渐升高来测量肺泡液体清除率。通过钾浓度和肺泡液体量的变化来测量钾的净转运。在钾浓度为0.3 mEq/L的实验中,YM934(10⁻⁴ M)使钾向肺泡腔的净流入增加了140%,同时肺泡液体清除率提高了60%。KATP通道阻滞剂格列本脲(10⁻⁴ M)抑制了YM934引起的钾转运流入增加及肺泡液体清除率升高。顶端钠摄取抑制剂氨氯吡咪(10⁻⁵ M)也阻断了YM934刺激引起的肺泡液体净清除率增加。这些结果表明,KATP通道开放剂可影响钾的转运以及液体通过人肺泡上皮的净向量移动。