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
Objective To determine whether Ca2+ activated Cl- current(Icl(Ca)) contributes to the functional remodeling of the failing heart.Methods Whole cell patch-clamp recording technique was employed to record the Icl(Ca) in cardiac myocytes enzymatically isolatedfrom rapidly pacing induced canine failing hearts at room temperature and compared that of the normal hearts (Nor).Results Thecurrent density of DIDS(200M)sensitive Icl(Ca) induced by intracellular Ca2+ release trigged by L-type Ca2+ current(Ica,L)wassignificantly decreased in heart failare(HE)cells compared to Nor cells.At membrane voltage of 20mV,the Icl(Ca) density was 3.02±0.54 pA/pF in Nor(n=6)vs.1.31±0.25 pA/pF in HF(n=8)cells,(P＜0.01),while the averaged Ica,L density did not show differencebetween two groups.The time constant of current decay of Icl(Ca) was similar in both types of cells.On the other hand,in intra cellularCa2+ clamped mode,where the[Ca2+];was maintained at 100nmol/L,Icl(Ca) density be increased significantly in HF cells when themembrane voltage at+30mV or higher.Conclusions Our results suggest that Icl(Ca) density was decreased in pacing induced failingheart but the channel function be enhanced.Impaired Ca2+ handing in HF cells rather than reduced,Icl(Ca) channel function itself may havecaused this abnormality.The Icl(Ca) density reduction might contribute to the prolongation of action potential in failing heart.The Icl(Ca)channel function up-rugulation is likely to cause cardiac arrhythmia by inducing a delayed after depolarization,when Ca2+ overloadoccurred in diastolic failing heart cells.