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Lin Xu,
Xu-Yong Li,
Yu Liu,
Hai-Tao Li,
Jing Chen,
Xiao-Yan Li,
Xue-Jun Jiang,
Gang Wu,
Yan-Hong Tang, Xi Wang,
Cong-Xin Huang
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ABSTRACT: L-type calcium current (I(Ca)) plays a critical role in excitation-contraction coupling (ECC). Unlike transient outward K(+) current (I(to)), it is controversial whether I(Ca) transmural gradient exists in left ventricle. Although previous studies have shown some evidences for I(Ca) heterogeneity, the mechanism is still unknown. In this study, the authors recorded I(Ca) from epicardial (EPI) and endocardial (ENDO) myocytes isolated from murine left ventricle using patch-clamp technique. It was found that I(Ca) density was obviously larger in EPI than in ENDO (7.3 ± 0.3 pA/pF vs. 6.2 ± 0.2 pA/pF, at test potential of +10 mV, P < 0.05). The characteristics of I(Ca) showed no difference between these two regions except for the fast inactivation time constants (9.9 ± 0.9 ms in EPI vs. 13.5 ± 0.9 ms in ENDO, at test potential of +10 mV, P < 0.05). In addition, it was explored the molecular mechanism underlying I(Ca) transmural gradient by Western blot. The authors demonstrated that a higher activity of CaMKII in ENDO cells induced more nuclear translocation of p65, a component of nuclear factor-kappa B (NF-kB). Consequently, p65 in ENDO inhibited more transcription of Cav1.2, the main encoding gene for L-type calcium channels (LTCCs). These results reveal a difference in CaMKII/p65 signal pathway between EPI and ENDO that underlies this mechanism of I(Ca) heterogeneity in murine left ventricle.
Molecular and Cellular Biochemistry 03/2011; 352(1-2):239-46. · 2.06 Impact Factor
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Qing-Yan Zhao,
He Huang,
Shu-Di Zhang,
Yan-Hong Tang, Xi Wang,
Yu-Guo Zhang,
Mohamed Salim,
Emmy Okello,
Hong-Ping Deng,
Sheng-Bo Yu,
Cong-Xin Huang
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ABSTRACT: The effects of ganglionated plexi (GP) ablation on atrial fibrillation (AF) inducibility and atrial autonomic innervation remodelling have not been elucidated.
Thirteen dogs were randomly divided into sham-operated group and GP ablation group. All animals underwent a right thoracotomy at the fourth intercostal space. Atrial fibrillation inducibility was assessed by burst rapid pacing at right atrium (RA). After anterior right GP and inferior right GP ablation, AF inducibility was assessed in the GP ablation group. The animals were allowed to recover for 8 weeks, after which, AF was measured again. The levels of atrial natriuretic peptide (ANP) in blood and atrial tissues were examined by radioimmunoassay. Immunocytochemical staining of cardiac nerves was performed in tissues from the dogs. Atrial fibrillation was induced easily in the GP ablation group after 8 weeks although AF was not observed in the sham-operated group, and after instant GP ablation. Compared with that in the sham-operated group, the levels of ANP in the blood and RA increased significantly 8 weeks after GP ablation (111.4 +/- 18.2 vs. 175.1 +/- 25.9; 184.9 +/- 36.3 vs. 299.1 +/- 32.5; P < 0.05). In the GP ablation group, the density of growth-associated protein 43-positive, tyrosine hydroxylase-positive, and choline acetyltransferase-positive nerves in the RA was 821 +/- 752, 481 +/- 627, and 629 +/- 644 per mm(2), respectively, which was significantly (P < 0.01) lower than the nerve density in sham-operated tissues (2590 +/- 841, 1752 +/- 605, and 3147 +/- 886 per mm(2), respectively).
Atrial autonomic innervations remodelling may be the mechanism of induced AF after GP ablation.
Europace 03/2010; 12(6):805-10. · 1.98 Impact Factor
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ABSTRACT: To investigate the effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins mRNA expressions in rabbits with heart failure (HF).
HF was induced by experimental aortic insufficiency and abdominal aortic constriction, HF animals were treated with oral apocynin (15 mg/d), a NADPH oxidase inhibitor or equal dose placebo. Eight weeks later, cardiac function was measured by echocardiography. Myocardial NADPH oxidase activity was evaluated by NADPH dependent superoxide production examined using superoxide dismutase-inhibitable cytochrome c reduction. Sarcoplasmic reticulum Ca(2+)ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phospholamban (PLB) and sodium-calcium exchanger (NCX) were determined by RT-PCR.
Rabbits with HF developed ventricular dilatation and cardiac dysfunction, as well as increase in myocardial NADPH oxidase activity, decreases in mRNA expression of SERCA2a, RyR2 and PLB, and increase in mRNA expression of NCX. Apocynin significantly reduced NADPH oxidase activity (P < 0.05), upregulated SERCA2a, RyR2 and PLB mRNA expressions (SERCA2a/GAPDH: 0.63 +/- 0.11 vs. 0.34 +/- 0.08, RyR2/GAPDH: 0.23 +/- 0.04 vs. 0.17 +/- 0.06, PLB/GAPDH:1.28 +/- 0.13 vs. 0.95 +/- 0.09, P < 0.05), downregulated NCX mRNA expression (NCX/GAPDH: 0.67 +/- 0.10 vs. 0.95 +/- 0.12, P < 0.05), and improved cardiac function [LVEF: (60.06 +/- 10.07)% vs. (38.87 +/- 3.31)%, LVFS: (30.12 +/- 6.56)% vs. (17.40 +/- 2.45)%, P < 0.05] in rabbits with HF.
NADPH oxidase inhibition improves cardiac function possibly by preventing abnormal alterations in myocardial calcium regulatory proteins in failing heart.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 10/2009; 37(10):883-6.
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ABSTRACT: Ghrelin is a newly discovered peptide as an endogenous ligand for the growth hormone secretagogue receptor, and has been demonstrated to exert beneficial effect in the cardiovascular system. In the present study, we investigated whether ghrelin administration could inhibit cardiac neural remodeling and sympathetic hyperinnervation after myocardial infarction. Sprague-Dawley rats underwent coronary ligation to induce myocardial infarction and receiving ghrelin chronically (100 microg/kg s.c., twice daily) or saline control for 4 weeks after onset of ischemia. Four weeks after treatment, rats were sacrificed. We examined the expression of nerve growth factor and never markers as well as the mRNA expressions of inflammatory mediators in the infarcted border and non-infarcted left ventricular free wall. We also examined the NF-kappaBp65 protein and I-kappaBalpha protein levels by Western blot analysis. Compared to the control group, ghrelin administration significantly decreased the density of nerve fibers with positive immunostaining for GAP43 and TH, and decreased NGF mRNA and protein levels in the infarcted border and the non-infarcted area. Ghrelin also significantly suppressed interleukin-1beta, tumor necrosis factor-alpha, and endothelin-l mRNA expression, and inhibited NF-kappaB activation. In conclusion, treatment with ghrelin inhibited neural remodeling and sympathetic hyperinnervation, the process that may be associated with the inhibition of proinflammatory response and NGF signaling.
European journal of pharmacology 08/2009; 618(1-3):52-7. · 2.59 Impact Factor
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ABSTRACT: The crista terminalis (CT) is known to initiate and maintain atrial arrhythmia, and is affected by autonomic tone, but the underlying mechanisms are poorly understood. This study sought to study the relation between autonomic innervation in CT and atrial arrhythmia.
Thirty adult canines were used in the present study. Tissues of the CT and the pectinate muscles (PM) were obtained from 10 dogs for electrophysiology studies. Furthermore, tissues of the superior CT, the inferior CT, and the PM were obtained from 10 dogs for immunohistochemistrical studies. Anti-growth-associated protein 43 (GAP43), anti-tyrosine hydroxylase (TH), and choline acetyltransferase (ChAT) antibodies for immunocytochemical staining of cardiac nerves were performed to test the densities of autonomic nerve. Densities of I K,ACh in the superior CT, the inferior CT, and the PM cells were measured by patch clamp in the other 10 dogs.
With the pacing cycle length decreased, the amplitude of delayed after depolarization (DAD) increased and DAD-induced triggered activity was induced in the CT but not in PM with norepinephrine administration. GAP-43 and TH-positive nerves in the superior CT and the inferior CT were all significantly higher than in the PM (GAP-43: 6,250 +/- 1,928 vs 1,247 +/- 747, 2,855 +/- 1,579 vs 1,247 +/- 747; TH: 3,140 +/- 1,240 vs 690 +/- 720, 1,210 +/- 980 vs 690 +/- 720; P < 0.01). Furthermore, the GAP-43 and TH-positive nerves in the superior CT were higher than in the inferior CT. However, there were no significant differences in ChAT-positive nerves and I K,ACh in the superior CT, the inferior CT, and the PM.
The higher densities of adrenergic nerve in the CT play an important role in the genesis of atrial arrhythmia.
Journal of Cardiovascular Electrophysiology 06/2009; 20(5):551-7. · 3.06 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is a common complication of myocardial infarction (MI). Angiotensin II receptor antagonists prevent the promotion and propagation of AF. However, the activation of the acetylcholine-regulated K(+) current (I(K,ACh)) in the atrium after MI and the effect of valsartan on I(K,ACh) are less understood.
Twenty-four adult rabbits were randomly divided into three groups: sham-operated, MI and MI plus valsartan administration (MI+valsartan). The sham-operated group received a median sternotomy without left ventricular coronary artery ligation. Both the MI group and the MI+valsartan group received a median sternotomy followed by ligation of the midpoint of the left ventricular coronary artery. The MI+valsartan group was administered oral valsartan for 12 weeks. After 12 weeks, the initiation of AF was measured by vagal stimulation followed by quick excision of the heart. I(K,ACh) in the left atrial myocardium was measured by the patch clamp technique.
AF was induced in four animals in the MI group, two in the sham-operated and two in the MI+valsartan groups, with the total AF duration expectedly longer in the MI group than in the sham-operated and MI+valsartan groups (38 s versus 9 s and 9 s, respectively). Furthermore, the mean (+/- SEM) density of I(K,ACh) increased significantly more in the left atrial myocardia of the MI group than in the sham-operated and the MI+valsartan groups (-13+/-0.42 pA/pF versus -9+/-0.38 pA/pF and -10+/-0.37 pA/pF, respectively at -100 mV; and 4.1+/-0.28 pA/pF versus 3.1+/-0.27 pA/pF and 3.3+/-0.27 pA/pF, respectively at 20 mV; P<0.05). However, there was no statistically significant difference in I(K,ACh) between the sham-operated group and the MI+valsartan group.
AF is associated with increased I(K,ACh) after MI. Inhibition of increased IK,ACh may be the mechanism by which valsartan prevents AF following MI.
The Canadian journal of cardiology 04/2009; 25(4):e115-8. · 3.36 Impact Factor
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ABSTRACT: To observe the prevalence of J wave in apparently healthy subjects in Wuhan.
The study subjects comprised of 1817 apparently healthy subjects (1131 males, mean age 46.38 +/- 15.81 years; 686 females, mean age was 42.77 +/- 14.15 years). ECG and routine medical examinations were performed. J wave was defined as a wave followed QRS complexes with amplitude of at least 0.05 mV and 0.03 s.
The overall incidence of J wave was 7.26%. The incidence of J wave in males was significantly higher than in females (10.53% vs. 1.87%, P < 0.01). The incidence of J wave in leads of inferior wall (II, III, avF), right wall (V(1 - 3)) and left wall (V(4 - 6)) was 4.57%, 0.50%, and 2.20%, respectively. J wave located in leads of inferior wall was more than in left and right walls (both P < 0.05). The incidence of J wave positively correlated with age (y = 0.1387x + 1.6318, r = 0.78, P < 0.01).
J wave is more likely seen in males and aged people and is more likely located in leads of inferior wall, than in leads of left and right walls.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 11/2007; 35(10):930-5.
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ABSTRACT: To investigate the relationship between the changes of the L-type calcium current (I(Ca, L)) and the calcium-activated transient outward chloride current (I(Cl, Ca)), and the repolarization characteristic of action potential in phase 1 under isoprenaline (ISO) stimulation in atrium myocytes of rabbit.
Atrium myocytes were obtained by enzymatic dissociation from a section of atrial free wall. The membrane currents and action potential were recorded by the whole-cell patch-clamp technique.
After recording I(Ca, L), atrium myocytes were perfused with ISO (1 micromol/L) immediately. Five minutes later, a transient outward current (I(to)) was significantly induced, and the peak of I(to) was gradually increased while I(Ca, L) gradually decreased with increasing in clamp voltage. The I(to) was resistant to 4-AP (3 mmol/L) but sensitive to DIDS (150 micromol/L, Cl(-) channel blocker). This current was blocked by CdCl(2) (200 micromol/L, Ca(2+) channel blocker). The elicited rate of I(to) was 91.67% (P < 0.05). (2) The shape of AP was like an inverse triangle with no plateau in Phase 2 after ISO (1 micromol/L) perfusion. Moreover, compared to the parameters of control group, APD(50) and APD(90) were significantly shortened from (65.4 +/- 4.2) ms and (95.8 +/- 3.8) ms to (12.8 +/- 3.8) ms and (27.0 +/- 4.7) ms, and reduced to 80.46% and 71.87%, respectively (P < 0.01, n = 12). 4-AP (3 mmol/L) had on obvious effect on the shape of AP, however, the plateau of AP in phase 2 was recovered by DIDS (150 micromol/L) perfusion, APD(50) and APD(90) were (41.1 +/- 4.5) ms and (79.6 +/- 3.4) ms respectively. Compared to the parameters of control group, there were no significant differences (P > 0.05, n = 12). These results indicated that ionic transport were changed by ISO perfusion in atrium myocytes and I(to) played an important role in the phase 1 repolarization of AP.
Before ISO administration, we could only observe I(Ca, L) in atrium myocytes of rabbit. After isoproterenol intervention, certain intracellular ionic consistency and membrane ionic channels were changed. Calcium activated chloride channel and I(to2) revealed obvious predominance which shorten APD significantly. Action potential showed a triangle with no plateau, suggesting an electrical remodeling in atrium myocytes. The remodeling of ionic channel is related possibly with the opening of Ca(2+)-activated Cl(-) current, which maybe the electrophysiological base of reentrant atrial tachycardia.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 09/2005; 33(9):843-7.
