Role Of Voltage-Gate Potassium Channel In Pulmonary Arterial Smooth Muscle Cells Of Pulmonary Hypertension Induced By Left-to-Right Shunt In Rats

Objective: To investigated the difference of voltage-gate potassium channel of pulmonary arterial smooth muscle cells resting membrane potential(Em),membrane current,current density and I-V curves between pulmonary arterial hypertension rats induced by left to right shunt and normotensive rats, and to analyze the role of Kv during the progress of pulmonary arterial hypertension.Methods:40 Male SD rats ,aged 6～7 weeks, weighted 180～200g were randomly divided into three groups : group A(control,n=10);group B(sham operated only group ,n=10):only open abdomen and expose abdominal aorta and inferior vena cava; group C( PAH model group, n=20):shunting from abdominal aorta and inferior vena cava to establish pulmonary arterial hypertension. After operation, these rats were raised by the same condition for 11 weeks. Mean pulmonary artery Pressure (mPAP) of each rat was measured by right cardiac catheterization procedure. Right ventricular hypertrophy index (RVHI) was calculated and expressed as the ratio of right ventricular mass to left ventricular plus septal mass[RV/(LV+S)]. Then the rats were exsanguinated and the intrapulmonary arteries were collected, single PASMC was obtained by acute enzyme separation method (collagenase I plus papain)and the conventional whole-cell patch technique was used to record resting membrane potential(Em), potassium ion current of voltage-gated potassium channel ,Compare the I-V curve between each group .Result: (1)The mPAP and RVHI of group C(PH model group) were significantly higher than that of group A(control group),group B(sham operated only group)(,P<0.01,respectively); The difference of the mPAP and RVHI were not significant,P>0.05.(2)The Em of group C [(-33±4.09)mV]was significantly higer than that of group A[(-48.1±4.54)mV], P<0.01; The Em of group B was [(-51.11±3.66)mV],compare with group A, The difference was not significant,P>0.05 .(3)The peak current at +50 mV of voltage-gated potassium channel : In group C [(64.80±8.4) pA/pF],it was significantly lower than that of group A [(120.85±11.66) pA/pF] and group B[(118. 03±10.18) pA/pF] (P<0.01, respectively); The difference between group B and group A was not significant,P>0.05 .(4) Compared with group A,group B, the I-V curve of group C was significantly downward shift; the difference of I-V curve between group A and group B was not significant,P>0.05.(5)The correlation of resting membrane potential and mPAP,RVHI had significantly positive correlation((P<0.001,respectively); but the correlation of membrane current,menbrane current density and mPAP,RVHI,resting membrane potential had significantly negative correlation(P<0.001,respecti -vely),and correlation coefficient all exceed -0.701.Conclusion: During the formation process of left-to-right shunt induced pulmonary arterial hypertension, with the step up of pulmonary arterial pressure, the Em of PASMC potassium channel was step up,The current density of Kv channel was decreased, I-V curve was shift downward. Suggested that the function of Kv channel was inhibited may be the mechanism of pulmonary arterial hypertension induced by left-to-right shunting.