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Differences of promethazine and terfenadine on ion channels in guinea pig ventricular myocytes

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Chinese Medical Journal 2006年第11期119卷 944-947页

作者： LI Xue-wen NIU Shuan-cheng ZHANG Xuan-ping Lü Ji-yuan BAI Feng ZHANG Ling WU Bo-wei First Hospital Shanxi Medical University Taiyuan 030001China Department of Pharmacology Shanxi Medical University Taiyuan 030001China Department of Physiology Shanxi Medical University Taiyuan030001China

Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes （TdP） like ventricular arrhythmia.^3 This may be due to the blockage on rectifier postassium current （Ik） of terfenadine, resulting in the prolongation of the action potential duration （APD） and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.^4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the lk and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.

关键词： promethazine terfenadine ion channels ventricular myocytes H1 receptor

Voltage- and Use-dependent Effect of 7-chlor-benzylte-trahydropalmatine on Sodium Currents in Guinea Pig ventricular myocytes

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1998年第3期18卷 137-140页

作者：阎升李新华姚伟星夏国瑾江明性 Department of Pharmacology Tongji Medical University Wuchan

The whole-cell patch-clamp technique was employed to obtain information about the voltage-dependence and kinetics of interaction of 7-chlor-benzylte-trahydropalmatine (7-Cl-BTHP) with cardiac sodium channels. 7-Cl-BTHP (30 mol/L) significantly decreased the peak sodium current (from 7. 8±1. 8 nA to 5. 3±1. 4 nA, P<0. 01, n=5), without producing a shift of the current-voltage curve. It shifted the inactivation curves of sodium current to hyperpolarized potentials, and the V(0.5) was shifted from - (82. 5±2. 5) mV to - (95±2.4) mV (P <0. 05, n=4). 7-Cl-BTHP produced a significant use-dependent effect that was proportional to the duration of the voltage step. In addition, 7-Cl-BTHP slowed the recovery of sodium channel from inactivation, which could explain its use-dependent effects on sodium current. The characteristics of 7-Cl-BTHP blockage suggest that this agent binds preferentially to inactivated sodium channels.

关键词： 7-chlor-benzyltetrahydropalmatine myocardium sodium channel current guinea pig ventricular myocytes

Mechanism for Muscarinic Inhibitory Regulation of the L-type Ca2 + Current in Cardiac ventricular myocytes

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中国心脏起搏与心电生理杂志 2004年第Z1期18卷 90-91页

作者：蒋彬杨向军惠杰蒋廷波宋建平刘志华苏州大学附属第一医院心内科 215006

　　Objective The autonomic nervous system plays a key role in regulating cardiac function by modifying heart rate, contractility and impulse. The parasympathetic neurotransmitter acetyl-choline and muscarinic agonist carbachol (Cch) inhibit excitation-contraction coupling in cardiac ventricular myocytes. Muscarinic agonists suppress adenylyl cyclase (AC) acitivity and,by reducing activation of the cAMP/protein kinase A (PKA)cascade, inhibit the L-type Ca2+ current (ICa(L) ). They also increase the content of cGMP by stimulating guanylyl cyclase (GC) activity. The role of nitric oxide (NO)/cGMP in muscarinic inhibition has undergone considerable scrutiny. The role of the NO/cGMP pathway in the inhibition of ICa(L) by Cch was examined in guinea-pig ventricular myocytes.……

关键词： ventricular myocytes autonomic nervous system muscarinic agonist cardiac function adenylyl cyclase nitric oxide heart rate

Characteristics of the Nonselective Cation Current (NSCCs) in Rabbit Left ventricular Epicardial, Midmyocardial and Endocardial myocytes

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South China Journal of Cardiology 2007年第4期8卷 187-192,215页

作者： Min Zong Xinchun Yang Xiulan Liu Liang Shi Taifeng Liu Cardiology Center Beijing ChaoYang hospital Affiliated to the Capital University of Medical Sciences Beijing 100020 China Department of Physiology and Biophysics College of Life Sciences Peking University Beijing 100871 China

Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventric- ular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current （INa-Ca） and late INa in M region （ deep subepicardial to midmyocardial）. Studies from our laboratory have found a new repolarization current-nonselective cation current （NSCCs） existing in rabbit fight ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp tech- niques. The permeability to Na^＋ , K^＋ , Li^＋ , Cs^＋ but not to Cl^- indicating that it was a nonselective cation current. Gd^＋3 （0. 1 mmol/1） and La^3＋（0. 1 retool/1 ） can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to - 80 mV, INa current density was （ -0. 44 ±0. 05） PA/PF in endocardial cells, （ -0. 12 ±0. 05） PA/PF in M cells and （ - 0. 28 ±0. 07） PA/PF in epicardial cells ; and with repolarization to ＋ 30 mV, INa, current density was （ 1.09 ± 0. 29） PA/PF in endocardial cells, （0. 38±0. 09） PA/PF in M cells and （0. 91 ± 0. 32） PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.

关键词： non-selective cation current ventricular myocytes epi-and endocardial myocytes M cells rabbi theart.

Sex Difference in the Repolarization Currents of Rabbit ventricular Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2005年第3期25卷 260-262页

作者：阮燕菲刘念周强李泱王琳 Department of Cardiology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, I_to, I_K,tail, I_K1 and I_Ca,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD_90 was longer in female rabbits (560.4±26.5 ms, n=15) than in male ones (489.0±20.7 ms, n=14), Pmyocytes, I_K,tail, I_to, I_K1 and I_Ca,L were 0.71±0.05 pA/pF (n=17), 8.28±1.03 pA/pF (n=18), 24.5±3.6 pA/pF (n=12) and 9.0±2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84±0.07 pA/pF (n=18), 8.60±1.20 pA/pF (n=18), 25.9±4.5 pA/pF (n=14) and 9.3±2.6 pA/pF (n=16) respectively. I_K,tail in female rabbits was significantly lower than that of male rabbits (P0.05). The lower I_K,tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.

关键词： patch clamp technique ventricular myocytes potassium current calcium current sex difference

Chromium(VI)-induced Production of Reactive OxygenSpecies, Change of Plasma Membrane Potential and Dissipation of Mitochondria Membrane Potential in Chinese Hamster Lung Cell Cultures

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Biomedical and Environmental Sciences 2001年第3期14卷 199-206页

作者： XIEYI ZHUANGZHI－XIONG DepartmentofToxicology ChinsesAcademyofPrventiveMedicineBeijing100050China ShenzhenCenter TianbeiRoad1SHenzhen518000China

Objective\ To examine whether Reactive Oxygen Species (ROS) is generated, and whether plasma membrane potential and mitochondrial membrane potential are depolarized in Chinese Hamster Lung (CHL) cell lines exposed to Cr (VI). Methods\ CHL cells were incubated with Cr(VI) at 10 μmol/L, 2.5 μmol/L, 0.65 μmol/L for 3 and 6 hours, respectively. The production of ROS was performed by using 2,7_dichlorofluorescin diacetate; The changes in plasma membrane potential were estimated using fluorescent cationic dye DiBAC4; And the changes in mitochondria membrane potential were estimated using fluorescent dye Rhodamine 123. Results\ The ROS levels in CHL cells increased in all treated groups compared with the control group (P<0.01); The plasma membrane potential and mitochondrial membrane potential in CHL cells dissipated after incubated with Cr(VI) at 10 μmol/L for 3 hours and 6 hours (P<0.01), at 2.5 μmol/L for 6 hours (P<0.01 or 0 05). Conclusion\ Cr(VI) causes the dissipation of plasma membrane potential and mitochondrial membrane potential in CHL cell cultures, and Cr(VI)_induced ROS may play a role in the injuries.

关键词： HYDROGEN-PEROXIDE FREE-RADICALS DNA-DAMAGE ventricular myocytes GENERATION REDUCTION CR(VI) 8-HYDROXYDEOXYGUANOSINE CARCINOGENICITY IDENTIFICATION

The Regulation Effects of β_2-AR on I_(NCX) in myocytes from Infarcted Rat Heart

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South China Journal of Cardiology 2009年第3期10卷 154-158页

作者：杨蕙伍卫邓春玉刘健 Department of Cardiology The First Municipal People's Hospital of Guangzhou

Objectives This study is designed to investigate the regulation effects of β2-adrenergic receptors （AR） on expression of the Na^± - Ca^2 ± exchanger （ INCX） in myocytes from the infarcted rat heart. Methods Twenty-eight adult Wistar rats were randomly divided into four groups ： the control group, the two weeks, four weeks and eight weeks post-myocardial infarction （post-MI） groups, respectively. The chest of rat was opened and a ligature was placed around the left anterior descending coronary artery. Rats in control group were sham-operated without the coronary artery ligation. After the operation, rats were fed for two, four or eight weeks respectively. myocytes were enzymatically disassociated by Langendorff perfusion. The whole cell-patch clamp recording technique was used to record INCX in specific pipette solution and superfusion according to the specific holding potential and command potential program. Results The INCX in ventricular myocytes from the border zone of infarcted myocardium increased significantly at eight weeks after MI （0. 51 ± 0. 12 pA/pF vs 1.07± 0. 21 pA/pF, P 〈0.05）. β2-AR agonist increased INcx more strongly in myocytes from post- MI heart than in controls. β2-AR antagonist attenuated the rise of INCX, strongly in myocytes from post-MI heart than in controls, whereas β1-AR onist. Conclusion The regulation effects of β2-AR on INCX in myocytes AR had closer relationship with the genesis of malignant arrhythmia afte

关键词： myocardial infarction β2 adrenergic receptor ventricular myocytes arrhythmia INCX

High intracellular Mg2+ affects upon the activities of L-type calcium channel in guinea-pig ven-tricular myocytes

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High intracellular Mg2+ affects upon the activities of L-typ...