Relationship between temperature and stimulation frequency in conduction block of amphibian myelinated axon

The temperature–frequency relationship in nerve conduction block induced by high-frequency, biphasic electrical current was investigated by computer simulation using an amphibian myelinated axon model based on Frankenhaeuser–Huxley (FH) equations. For an axon of diameter 10 μm, the minimal blocking frequency was changed from 6 to 3 kHz as the temperature was decreased from 37°C to 15°C. The maximal blocking temperature below which the axon could be blocked was increased from 22°C to 37°C as the stimulation frequency was increased from 4 to 8 kHz. The maximal blocking temperature was not influenced by axon diameter. Simulation analysis also revealed that activation of potassium channels might determine the temperature–frequency relationship. This study indicates that temperature might be one of the factors that cause the frequency discrepancy as reported in previous animal studies. Action Editor: Alain Destexhe     

Quaternary ammonium ion blockade of IK in nerve axons revisited. Open channel block vs. state independent block

The mechanism of blockade of the delayed rectifier potassium ion channel in squid giant axons by intracellular quaternary ammonium ions (QA) appears to be remarkably sensitive to the structure of the blocker. TEA, propyltriethyl-ammonium (C₃), and propyltetraethylammonium (TAA-C₃) all fail to alter the deactivation, or tail current time course following membrane depolarization, even with relatively large concentrations of the blockers, whereas butyltriethylammonium (C₄), butyltetraethylammonium (TAA-C₄), and pentytriethyammonium (C₅) clearly do have such an effect. The relative electrical distance of blockade for all of these ions is 0.25–0.3 from the inner surface of the membrane. The observations concerning TEA, C₃, and TAAC₃ suggest that these ions can block the channel in either its open or its closed state. The results with C₄, TAA-C₄, and C₅ are consistent with the open channel block model. Moreover, the sensitivity of block mechanism to the structure of the blocker suggests that the gate is located close to the QA ion binding site and that TEA, C₃, and TAA-C₃ do not interfere with channel gating, whereas C₄, TAA-C₄, C₅, and ions having a longer hydrophobic tail than C₅ do have such an effect. The parameters of block obtained for all QA ions investigated were unaffected by changes in the extracellular potassium ion concentration.The author gratefully acknowledges Paul Guth of Cambridge Chemical for custom synthesis of the C _n compounds used in this study, Michael Rogawski for helpful discussion of this work, and Adam Sherman of Alembic Software and Vijay Kowtha for technical assistance in data acquisition and analysis.     

千频交流电刺激在外周神经传导阻断中的作用

感觉、运动或自主神经系统的异常病理活动与疼痛和痉挛等多种神经机能障碍有关。千频交流电（kilohertz frequency alternating current，KHFAC）刺激是一种阻断异常病理活动在外周神经内传导的有效方法，它在缓解相关神经机能障碍方面具有临床应用潜力。KHFAC产生的神经传导阻断受千频信号波形和参数、阻断电极设置和位置以及神经纤维类型和直径等因素影响，具有快速性、可控性、可逆性、局部作用和副作用小的特点。但是，在产生完全传导阻断前，KHFAC首先在靶向神经上激活一簇高频初始放电，这种初始响应可能导致肌肉抽搐或疼痛感。同时，在撤去KHFAC后处于阻断状态的靶向神经需要经历一段时间才能恢复正常传导能力，这是该技术导致的后续效应。目前，关于KHFAC阻断神经传导的生物物理机制假说包括千频信号诱发K⁺通道激活和Na⁺通道失活。本文首先介绍了KHFAC技术的电生理实验研究方法和计算模型仿真方法，然后综述目前关于KHFAC作用下神经传导阻断的研究进展，重点论述初始响应特性及消除方法、传导阻断的后续效应、刺激波形和参数的影响、电极设置与位置的影响以及该技术潜在的临床应用，同时归纳KHFAC阻断神经传导的生物物理机制，最后对该技术未来的相关研究进行展望。     

Rate and irregularity of electrical activation during atrial fibrillation affect myocardial NGF expression via different signalling routes

An irregular ventricular response during atrial fibrillation (AF) has been shown to mediate an increase in sympathetic nerve activity in human subjects. The molecular mechanisms remain unclear. This study aimed to investigate the impact of rate and irregularity on nerve growth factor (NGF) expression in cardiomyocytes, since NGF is known to be the main contributor to cardiac sympathetic innervation density. Cell cultures of neonatal rat ventricular myocytes were electrically stimulated for 48 h with increasing rates (0, 5 and 50 Hz) and irregularity (standard deviation (SD) = 5%, 25% and 50% of mean cycle length). Furthermore, we analyzed the calcineurin-NFAT and the endothelin-1 signalling pathways as possible contributors to NGF regulation during arrhythmic stimulation. We found that the increase of NGF expression reached its maximum at the irregularity of 25% SD by 5 Hz (NGF: 5 Hz 0% SD = 1 vs. 5 Hz 25% SD = 1.57, P < 0.05). Specific blockade of the ET-A receptor by BQ123 could abolish this NGF increase (NGF: 5 Hz 25% SD + BQ123 = 0.66, P < 0.05). High frequency electrical field stimulation (HFES) with 50 Hz decreased the NGF expression in a significant manner (NGF: 50 Hz = 0.55, P < 0.05). Inhibition of calcineurin-NFAT signalling with cyclosporine-A or 11R-VIVIT abolished the HFES induced NGF down-regulation (NGF: 50 Hz + CsA = 1.14, P < 0.05). In summary, this study reveals different signalling routes of NGF expression in cardiomyocytes exposed to increasing rates and irregularity. Whether this translates into different degrees of NGF expression and possibly neural sympathetic growth in various forms of ventricular rate control during AF remains to be elucidated in further studies.