Roles of voltagegated potassium channels in progression of chronic hypoxic pulmonary hypertension

AIM:To observe the influence of chronic hypoxia on the activity of voltagegated potassium channel in pulmonary artery smooth muscle cells of rats and its roles in the progression of chronic pulmonary hypertension. METHODS: Fifty male Sprague Dawley rats were randomly allocated into normoxic group (n=10) and chronic hypoxic groups. The chronic hypoxic groups were randomly allocated into four subgroups (n=10, respectively) according to the chronic hypoxic periods. The chronic hypoxic subgroups were kept in a hypoxic environmental chamber 8 h/day for 5, 10, 20, and 30 days, respectively, while the normoxic group was kept in room air. The mean pulmonary arterial pressure (mPAP) and the current of voltagegated potassium channel (IK) in pulmonary artery smooth muscle cells were measured using conventional whole cell patchclamp technique. RESULTS: No significant difference was observed in the density of IK (at +60 mV) and the IV relationship between normoxic group and the group exposed to chronic hypoxia for 5 days (P>005), whereas significant differences were found between the normoxic group and the group exposed to chronic hypoxia for 10 days (P<005). With the prolonged exposure to hypoxia, the peak density of IK decreased gradually at +60 mV. In normoxic rats, the mPAP was significantly increased after exposure to chronic hypoxia for 10 days (P<005) and prolonged exposure to hypoxia further increased the mPAP. The mPAP was negatively correlated with the density of IK (r=-089769, P<001). CONCLUSION: Exposure to chronic hypoxia may cause decreased activity of voltagegated potassium channel, which leads to hypoxic pulmonary vasoconstriction. This mechanism plays an important role in the progression of chronic pulmonary hypertension.