Effects of Volsartan on Transmural Heterogeneous Changes of Transient Outward Potassium Currents in Hypertrophic Cardiomyocytes in Rabbits

The transmural heterogeneous changes of transient outward potassium currents (Ito) in rabbit hypertrophic cardiaomyocytes and the effects of long-term prophylactic treatment with volsartan were investigated. Rabbits were divided into hypertrophy group (left ventricular hypertrophy induced by partial ligation of abdominal aorta), vol-treated group (volsartan was administrated after the ligation), and control group (sham operated). Myocytes were isolated by a two-step enzymatical method. The sub-endocardial (Endo) and sub-epicardium (Epi) tissues were separated from midmyocardium (Mid) with a razor. Whole-cell patch-clamp technique was used to record potassium currents. The results showed that membrane capacitance was larger in hypertrophic cells than those in control and vol-treated cells (P<0.01 vs control cells, n=30). The densities of Ito in hypertrophic cells were reduced by sub-epicardium (Epi) (27.8±2.9) %, midmyocardium (Mid) (41.0±4.7) %, and sub-endocardium (Endo) (20.3±3.4) % compared with those in control cells. The decrease of Ito density was more pronounced in Mid than in Epi and Endo (P<0.01 vs Epi or Endo). There were no significant differences in Ito densities between vol-treated group and control group in three layers separately. In conclusion, volsartan can inhibit the transmural heterogeneous changes of Ito in left ventricular hypertrophic cardiomyocytes in rabbit.

Electrical heterogeneity of canine right ventricular transient outward potassium currents

Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (I to1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent I to1. Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the I to1 values of the three cell types. Results At 37℃ and using 0.2 Hz and +70 mV depolarizing test potentials, the average peak I to1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with I to1 in Epi cells and M cells, the average peak I to1 in Endo cells was very low, averaged (470±130) pA. Conclusions These results suggest that there are evident differences and potent gradients in I to1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.

Two outward potassium current types are expressed during the neural differentiation of neural stem cells

The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S ＋ G2/M phase was high. However, the ratio of cells in the S ＋ G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp re- cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo- campus could be cultured and induced to differentiate into functional neurons under defined condi- tions in vitro. The differentiated neurons expressed two types of outward potassium ion cur＇ents similar to those of mature neurons in vivo.

Characteristics of Transient Outward Potassium Channel Exposed to 3 mT Static Magnetic Field

Acutely isolated mouse hippocampal CA3 pyramidal neurons were exposed to 3 mT static magnetic field,and the characteristics of transient outward K+ channel were studied using the whole-cell patch-clamp technique.The experiment revealed that the amplitude of transient outward potassium channel current was reduced.The maximum activated current densities of control group and exposure group were 163.62±20.68 pA/pF and 98.74±16.57 pA/pF(n=12,P<0.01) respectively.The static magnetic field exposure affected the activation and inactivation process of transient outward potassium channel current.Due to the magnetic field exposure,the half-activation voltage of the activation curves changed from 5.59±1.96 mV to 27.87±7.24 mV(n=12,P<0.05) ,and the slope factor changed from 19.43±2.11 mV to 25.87±4.22 mV(n=12,P<0.05) .The half-inactivation voltage of the inactivation curves also changed from-56.09±0.89 mV to-57.16±1.10 mV(n=12,P>0.05) and the slope factor of the inactivation curves from 8.69±0.80 mV to 10.87±1.02 mV(n=12,P<0.05) .The results show that the static magnetic field can change the characteristics of transient outward K+ channel,and affect the physiological functions of neurons.

Silencing gamma-aminobutyric acid A receptor alpha 1 subunit expression and outward potassium current in developing cortical neurons

We used RNA interference （RNAi） to disrupt synthesis of the cortical neuronal y-aminobutyric acid A receptor （GABAAR） al in rats during development, and measured outward K＋ currents during neuronal electrical activity using whole-cell patch-clamp techniques. Three pairs of small interfering RNA （siRNA） for GABAAR al subunit were designed using OligoEngine RNAi software. This siRNA was found to effectively inhibited GABAAR al mRNA expression in cortical neuronal culture in vitro, but did not significantly affect neuronal survival. Outward K^currents were decreased, indicating that GABAAR al subunits in developing neurons participate in neuronal function by regulating outward K＋ current.

The ionic mechanisms of long QT interval in diabetic rabbits

Objective Abnormal QT prolongation associated with arrhythmias is considered the major cardiac electrical disorder and a significant predictor of mortality in diabetic patients. The precise ionic mechanisms for diabetic QT prolongation remained unclear. The present study was designed to analyze the changes of ventricular repolarization and the underlying ionic mechanisms in diabetic rabbit hearts. Methods Diabetes was induced by a single injection ofalloxan （145mg/kg, Lv. ）. After the development of diabetes （10 weeks）, ECG was measured. Whole-cell patch-clamp technique was applied to record the action potential duration （APD50, APD90）, slowly activating outward rectifying potassium current （IKs）, L-type calcium current （ICa-L） and inward rectifying potassium current （IK1）. Results The action potential duration （APD50 and APD90） of ventricular myocytes was obviously prolonged from 271.5＋32.3 ms and 347.8＋36.3 ms to 556.6~72.5 ms and 647.9~72.2 ms respectively （P〈 0.05）. Meanwhile the normalized peak current densities of IKs in ventricular myocytes investigated by whole-cell patch clamp was smaller in diabetic rabbits than that in control group at test potential of＋50mV （1.27~0.20 pA/pF vs 3.08~0.67 pA/pF, P〈0.05）. And the density of the ICa-L was increased apparently at the test potential of 10 mV （-2.67~0.41 pA/pF vs -5.404-1.08 pA/pF, P〈0.05）. Conclusion Ventricular repolarization was prolonged in diabetic rabbits, it may be partly due to the increased L-type calcium current and reduced slow delayed rectifier K＋ current （IKs） （J Geriatr Cardio12010; 7：25-29）.

Differential effects of d,l-sotalol and d-sotalol on isoproterenol increased delayed rectifier outward potassium current in guinea pig myocytes

Objective Catecholamines antagonize the clinical efficacy of pure class Ⅲ antiarrhythmic agents in vivo. The antiarrhythmic agent d, l sotalol has β adrenergic blocking properties and class Ⅲ activity. However, its d isomer without β blockade has been shown to exert significant proarrhythmia. To determine the role of β adrenergic blocking properties of d, l sotalol on its antiarrhythmic effect, we compared the effects of d, l sotalol and d sotalol on delayed rectifier K + outward current in the presence of isoproterenol at different concentrations. Methods Time dependent delayed rectifier K + outward currents, I K (I Kr and I Ks ) and tail current (I K tail ) were measured in isolated guinea pig myocytes using the whole cell configuration of the patch clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of Department of Cardiology, University Hospital Heidelberg, Germany (Yao XZ, Yannoulis NC, Kiehn J and Brachmann J) 40 mV in three experimental protocols [control, isoproterenol (10 9 -10 6 mol/L), and isoproterenol (10 9 -10 6 mol/L) plus either d, l sotalol (10 4 mol/L) or d sotalol (10 4 mol/L)]. I K tail currents were measured upon repolarization to 40 mV. Results Isoproterenol significantly inreased I K and I K tail in a concentration dependent manner. I K was significantly amplified in the presence of isoproterenol (10 9 -10 6 mol/L) plus d sotalol. At 10 8 mol/L isoproterenol, I K was increased by 92.3%±23.7% before and 54.3%±13.4% after d sotalol. In contrast, d, l sotalol strongly suppressed the effect of isoproterenol on I K, and compared to control, I K was decreased by 35.6%±8.1% at 10 8 mol/L isoproterenol. Conclusions The β adrenergic blocking property of d, l sotalol maintains delayed rectifier K + outward current block in the presence of isoproterenol in guinea pig myocytes. This may result in its supperior antiarrhythmic efficacy compared to d sotalol.

J Wave Syndromes： A Decade of Progress

Objective： The objective was to provide a brief history of J wave molecular, ionic, cellular mechanisms, and clinical features. We will clinical research for J wave syndromes. syndromes and to summarize our current understanding of their also discuss the existing debates and further direction in basic and Data Sources： The publications on key words of＂J wave syndromes＂, ＂early repolarization syndrome （ERS）＂, ＂Brugada syndrome （BrS）＂ and ＂ST-segment elevation myocardial infarction （STEMI）＂ were comprehensively reviewed through search of the PubMed literatures without restriction on the publication date. Study Selection： Original articles, reviews and other literatures concerning J wave syndromes, ERS, BrS and STEMI were selected. Results： J wave syndromes were firstly defined by Yah et al. in a Chinese journal a decade ago, which represent a spectrum of variable phenotypes characterized by appearance of prominent electrocardiographic J wave including ERS, BrS and ventricular fibrillation （VF） associated with hypothermia and acute STEMI. J wave syndromes can be inherited or acquired and are mechanistically linked to amplification of the transient outward current （I ）-mediated J waves that can lead to phase 2 reentry capable of initiating VF. Conclusions： J wave syndromes are a group of newly highlighted clinical entities that share similar molecular, ionic and cellular mechanism and marked by amplified J wave on the electrocardiogram and a risk of VF. The clinical challenge ahead is to identify the patients with J wave syndromes who are at risk for sudden cardiac death and determine the alternative therapeutic strategies to reduce mortality.

Effect of Cu^2＋ on K^＋ Current in Acutely Isolated Rat Hippocampal Neurons by Whole Cell Patch Clamp Technique

Using the whole cell patch clamp technique, the effect of Cu^2＋on transient outward K^＋current （/to） and delayed rectifier K^＋ current （Idr） was studied in acutely isolated rat hippocampal neurons.Ito and Idr were increased when the concentration of Cu^2＋ was lower than 2 × 10^-5 and 10^-5 tool/L, respectively, and increased ratio was decreased with increasing Cu^2＋concentration in the bath solutions. When the concentration continued to increase to 5× 10^-5 and 2 × 10^- 5 mol/L, the currents were hardly changed, while the concentration was more than 10^-4 and 5 × 10^-5 mol/L, the currents were inhibited remarkably. Cu^2＋ （10^-5 mol/L） did not affect the activation and inactivation process of Ito. The activation curve of Idr was shifted toward positive potential, but 10^-5 mol/L Cu^2＋did not affect slope factor. According to these results, it was considered that Cu^2＋at low concentration in the bath solution could promote Ito and Idr while at high concentration could inhibit them, and change of amplitude was different with different membrane voltage. Conclusion was drawn： Cu^2＋may be involved in the pathophysiologic mechanism of diseases with neuropathological components.