Research Progress of Sodium Channel and Its Anti-arrhythmic Drugs

With the acceleration of population aging,heart disease has been a high priority,and cardiac ion channel research has been one of the hot spots in the field,Sodium ion channels,as the most important class,have been widely concerned.Therefore,this paper briefly introduces and discusses three aspects of the structure and function of sodium ion channels and the development of drug research.

Atrial fibrillation in obstructive sleep apnea

Atrial fibrillation(AF) is a common arrhythmia with rising incidence.Obstructive sleep apnea(OSA) is prevalent among patients with AF.This observation has prompted significant research in understanding the relationship between OSA and AF.Multiple studies support a role of OSA in the initiation and progression of AF.This association has been independent of obesity,body mass index and hypertension.Instability of autonomic tone and wide swings in intrathoracic pressure are seen in OSA.These have been mechanistically linked to initiation of AF in OSA patients by lowering atrial effective refractory period,promoting pulmonary vein discharges and atrial dilation.OSA not only promotes initiation of AF but also makes management of AF difficult.Drug therapy and electrical cardioversion for AF are less successful in presence of OSA.There has been higher rate of early and overall recurrence after catheter ablation of AF in patients with OSA.Treatment of OSA with continuous positive airway pressure has been shown to improve control of AF.However,additional studies are needed to establish a stronger relationship between OSA treatment and success ofAF therapies.There should be heightened suspicion of OSA in patients with AF.There is a need for guidelines to screen for OSA as a part of AF management.

Management of ventricular tachycardia storm in patients with structural heart disease

Electrical storm(ES) is a medical emergency characterized by repetitive episodes of sustained ventriculararrhythmias(VAs) in a limited amount of time(at least 3 within a 24-h period) leading to repeated appropriate implantable cardioverter defibrillator therapies. The occurrence of ES represents a major turning point in the natural history of patients with structural heart disease being associated with poor short-and longterm survival particularly in those with compromised left ventricular ejection fraction(LVEF) that can develop hemodynamic decompensation and multi-organ failure. Management of ES is challenging with limited available evidence coming from small retrospective series and a substantial lack of randomized-controlled trials. In general, a multidisciplinary approach including medical therapies such as anti-arrhythmic drugs, sedation, as well as interventional approaches like catheter ablation, may be required. Accurate patient risk stratification at admission for ES is pivotal and should take into account hemodynamic tolerability of VAs as well as comorbidities like low LVEF, advanced NYHA class and chronic pulmonary disease. In high risk patients, prophylactic mechanical circulatory support with left ventricular assistance devices or extracorporeal membrane oxygenation should be considered as bridge to ablation and recovery. In the present manuscript we review the available strategies for management of ES and the evidence supporting them.

Frequency- and state-dependent blockade of human ether-a-go-go-related gene K^＋ channel by arecoline hydrobromide

Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.