ABSTRACT
Objective To investigate the characteristics of different electrophysiology of Ca2+-activated Cl-channels (ClCa) in pulmonary arterial smooth muscle cells (PASMCs) between pulmonary arterial hypertension (PAH) rats induced by left-to-right shunt and normotensive rats,and to study its possible role in the progress of PAH induced by high pulmanry blood flow.Methods Forty SD rats were randomly divided into 3 groups:control group (n =10),sham group (n =10),PAH model group (n =20).After molding,the rats were raised in the same condition for 11 weeks.Right ventricular systolic pressure (RVSP) of each rat was measured by right cardiac catheterization procedure.Right ventricular hypertrophy index (RVHI) was calculated.Single PASMC was obtained by acute enzyme separation method and the conventional whole-cell patch clamp technique was used to record the resting membrane potential (Em),ClCa and current density.The Ⅰ-Ⅴ curve between each group were compared.Results Compared with control group and sham group,the Ⅰ-Ⅴ curve about Itail of PAH model group was significantly shift downward; the difference between control group and sham group was not significant.There were positive correlations between Em and RVSP,RVHI (all P ＜ 0.01),and negative correlations between Itail and RVSP,RVHI and Em(all P ＜ 0.01).Conclusions During the formation process of left-to-right shunt induced PAH,with the step up of pulmonary arterial pressure,the Em of PASMCs stepping up.The absolute value of current density of inward ClCa currents was increased,and its Ⅰ-Ⅴ curve was shift downward.These suggest that the change of ClCa currents may play a role in the PAH induced by left-to-right shunting.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the electrophysiological changes of voltage-gate potassium channel (Kv) of pulmonary arterial smooth muscle cells of pulmonary arterial hypertension in rats induced by left to right shunt, and to analyze the role of Kv during the progress of pulmonary arterial hypertension.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into three groups, group A (control, n = 10), group B (sham operated only group, n = 10), and group C (PAH model group, n = 20). Mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) of each rat were measured, single pulmonary artery smooth muscle cell (PASMC) was obtained by acute enzyme separation method (collagenase I plus papain) and the conventional whole-cell patch clamp technique was used to record resting membrane potential (Em), potassium ion current of voltage-gated potassium channel, the I-V curve between each 2 groups was compared, and correlation of each parameter was analyzed.</p><p><b>RESULT</b>(1) The mPAP and RVHI of group C were significantly higher than those of group A and group B (P < 0.01, respectively). (2) The Em of group C [(-33.00 ± 4.09) mV] was significantly higher than that of group A [(-48.10 ± 4.54) mV] and group B [(-51.11 ± 3.66) mV], P < 0.01. (3) The peak current at +50 mV of voltage-gated potassium channel: in group C [(64.80 ± 8.40) 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). None of the parameters showed any significant difference between group A and group B (P > 0.05 for all comparisons). (4) Compared with group A and group B, the I-V curve of group C significantly downward shifted (P < 0.01, respectively). The difference in I-V curve between group A and group B was not significant, P > 0.05. (5) The correlation of resting membrane potential and mPAP and RVHI had significantly positive correlation (P < 0.001, respectively); but the correlation of membrane current, membrane current density and mPAP, RVHI and resting membrane potential had significantly negative correlation (P < 0.001, respectively).</p><p><b>CONCLUSION</b>During the formation process of left-to-right shunt induced pulmonary arterial hypertension, function of Kv channel was inhibited, suggesting that Kv channel may be the mechanism of pulmonary arterial hypertension induced by left-to-right shunting.</p>
Subject(s)
Animals , Male , Rats , Hypertension, Pulmonary , Metabolism , Muscle, Smooth, Vascular , Metabolism , Patch-Clamp Techniques , Potassium , Metabolism , Potassium Channels, Voltage-Gated , Metabolism , Pulmonary Artery , Metabolism , Rats, Sprague-DawleyABSTRACT
Pulmonary artery hypertension (PAH) is a combination of factors caused abnormal pulmonary hemodynamics.Pulmonary vascular resistance (PVR) progressive as clinical features of PAH.In recent years,studies had shown that pulmonary artery smooth muscle cell membrane potassium channels at the time of PAH and pulmonary vasoconstriction (HPV) and vascular remodeling were closely related to potassium channel in the article on the role of PAH in progress of the study review.