Role of Voltage-gated Potassium Channels in Pathogenesis of Chronic Pulmonary Heart Disease

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2013-10, Vol.33 (5), p.644-649
• Main Author: 柯琴梅 吴霁 田莉 李伟 杜以梅
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - physiology; Cell Hypoxia - physiology; Cells, Cultured; Hypertrophy, Right Ventricular - physiopathology; Hypoxia - physiopathology; Male; Medicine; Medicine & Public Health; Membrane Potentials - physiology; Myocytes, Smooth Muscle - physiology; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated - physiology; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Pulmonary Heart Disease - physiopathology; Random Allocation; Rats; Rats, Sprague-Dawley; SD大鼠; Time Factors; Vasoconstriction - physiology; 发病机制; 心脏疾病; 慢性; 电压门控; 肺动脉平滑肌细胞; 肺心病; 钾通道
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1174-z

The influence of hypoxia on the activity of voltage-gated potassium channel in pulmonary artery smooth muscle cells （PASMCs） of rats and its roles in the pathogenesis of chronic pulmonary heart disease were investigated. Eighty male Sprague-Dawley rats were randomly allocated into control group （n=10）, acute hypoxic group （n=10）, and chronic hypoxic groups （n=60）. The chronic hypoxic groups were randomly divided into 6 subgroups （n=10 each） according to the chronic hypoxic periods. The rats in the control group were kept in room air and those in acute hypoxic group in hypoxia envi- ronmental chamber for 8 h. The rats in chronic hypoxic subgroups were kept in hypoxia environmental chamber for 8 h per day for 5, 10, 15, 20, 25, and 30 days, respectively. The mean pulmonary arterial pressure （mPAP）, right ventricular hypertrophy index （RVHI）, and the current of voltage-gated potas- sium channel （IK） in PASMCs were measured. Results showed that both acute and chronic hypoxia could decrease the IK in PASMCs of rats and the I-V relationship downward shifted to the right. And the peak Ir density at ＋60mV decreased with prolongation of hypoxia exposure. No significant difference was noted in the density oflK （at ＋60 mV） and I-V relationship between control group and chronic hy- poxic subgroup exposed to hypoxia for 5 days （P〉0.05）, but there was a significant difference between control group and chronic hypoxic subgroup exposed to hypoxia for 10 days （P〈0.05）. Significant dif- ferences were noted in the IK density （at ＋60 mV） and I-V relationships between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days （P〈0.01）. Compared with con- trol rats, the mPAP and RVHI were significantly increased after chronic exposure to hypoxia for 10 days （P〈0.05）, which were further increased with prolongation of hypoxia exposure, and there were signifi- cant differences between control group and chronic hypoxic subgroups exposed to hypoxia for 20 days and 30 days （P〈0.01）. Both the mPAP and the RVHI were negatively correlated with the density OflK （r---0.89769 and -0.94476, respectively, both P〈0.01）. It is concluded that exposure to hypoxia may cause decreased activity of voltage-gated potassium channel, leading to hypoxia pulmonary vasocon- striction （HPV）. Sustained HPV may result in chronic pulmonary hypertension, even chronic pulmonary heart disease, contributing to the pathogenesis of chronic pulmonary heart disease.