Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium

Objective Allocryptopine （ALL） is an effective alkaloid of Corydalis decumbens （Thunb.） Pers. Papaveraceae and has proved to be an- ti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current （Ito） and slow delayed rectifier potassium current （IKs）. Methods The monophasic action potential （MAP） technique was used to record the MAP duration of the epicardium （Epi）, myocardium （M） and endocardium （Endo） of the rabbit heart and the whole cell patch clamp was used to record/to and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization （TDR） in rabbit transmural ventricular wall. ALL decreased the current densities of/to and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation ofIto in M layers and partly inhibit the channel openings of/to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of tmnsmural inhibition of/to and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.

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.

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.

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.