Poly-l-aspartic acid protects cultured human proximal tubule cells against aminoglycoside-induced electrophysiological alterations

Cultured human proximal tubule cell monolayers maintained on permeable supports were treated simultaneously with the aminoglycoside antibiotic, gentamicin, and poly- -aspartic acid (PAA), an inhibitor of aminoglycoside nephrotoxicity. Following 4 days of exposure, cell monolayers were placed into Ussing chambers to allow monitoring of transepithelial electrical properties. For each of the three cell isolatation examined, aminoglycoside-induced alterations in electrogenic transport, reflected by changes in short-circuit current (Isc), as well as alterations in paracellular properties, indicated by changes in transepithelial electrical resistance (R_T), were diminished in the presence of PAA. Alterations resulting from selective basolateral exposure to gentamicin were unchanged in the case of apically applied PAA and attenuated only when PAA acid was added basolaterally. This is the first demonstration of PAA inhibition of aminoglycoside-induced cellular alterations involving human cells.     

Passive electrical properties of motoneurons in aged cats following axotomy

The objective of this study was to determine whether the aging process influences the changes in the electrophysiological properties of motoneurons that occur as a consequence of axotomy. Accordingly, using intracellular recording and stimulating techniques, the basic electrical properties of control (unaxotomized) and axotomized spinal cord motoneurons of aged cats were determined. Compared with control motoneurons, axotomized motoneurons exhibited increases in input resistance (R_in), membrane time constant (τ_b) and the equalizing time constant (τ_c). While the electrotonic length (L) remained unchanged, axotomy induced a decrease in the total cell capacitance (C_cell. The post-axotomy reduction of C_cell indicates that the motoneuron surface area was reduced and the increased membrane time constant indicates that there was an increase in membrane resistivity (R_m). The post-axotomy conservation of L accompanied by an increase in R_m suggests that aged axotomized motoneurons undergo geometrical changes. Furthermore, calculations based on cable theory suggest that the diameter of the equivalent cylinder (d) decreased following axotomy, whereas the equivalent cylinder length (l) remained unaffected. It is concluded that axotomy produces significant alterations in the soma-dendritic portion of aged spinal motoneurons, as indicated by the changes found in their passive electrophysiological properties, and that the pattern of the response that occurs in axotomized motoneurons of adult cats is also present in axotomized motoneurons of aged animals.     

Inhibition of rat hippocampal excitability by the plant alkaloid 3-acetylaconitine mediated by interaction with voltage-dependent sodium channels

The effects of the Aconitum alkaloid 3-acetylaconitine on neuronal activity were investigated in the slice preparation and on cultivated neurons of rat hippocampus by extracellular and patch-clamp recordings, respectively. 3-Acetylaconitine (0.01–1 μM) diminished the orthodromic and antidromic population spike in a concentration-dependent manner. The inhibitory action of the drug was preceded by a transiently enhanced excitability. The latency of onset of the inhibition was accelerated by increased stimulation frequency, whereas recovery during washout of the alkaloid was accelerated by decreased stimulation frequency. Moreover, the inhibitory effect of 3-acetylaconitine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors by bicuculline (10 μM) or by a nominal Mg²⁺-free bathing medium. In accordance with the activity-dependent mode of action, this compound abolished the synaptically evoked population spikes in the presence of bicuculline or nominal Mg²⁺-free bathing medium, respectively. Whole-cell patch-clamp recordings revealed an interaction of 3-acetylaconitine with the voltage-dependent sodium channel. At a concentration of 1 μM, 3-acetylaconitine did not affect the peak amplitude of the sodium current, but shifted the current-voltage relationship in the hyperpolarized direction such that sodium currents were already activated at the resting potential. Received: 22 July 1996 / Accepted: 14 October 1996     

不同浓度的金属硫蛋白对离体豚鼠乳头肌缺氧、复氧电生理特性的影响

为探讨金属硫蛋白（MT）对豚鼠乳头肌缺血再灌注损伤所致心律失常的影响，利用标准玻璃微电极技术，采用缺氧及复氧豚鼠乳头肌模型，模拟体内缺血再灌注损伤，观察不同浓度MT对豚鼠乳头肌电生理特性的影响。结果显示低浓度的MT（0．002mmol／L）对正常及缺氧和复氧豚鼠乳头肌的动作电位（AP）有关参数及自律性均无影响；中等浓度的MT（0．02mmol／L）仅使正常乳头肌的AP复极达50％时程（APD50）缩短24％（P＜0．05），但使缺氧乳头肌的AP复极达20％时程（APD20）、APD50和AP复极达90％时程（APD90）分别缩短68％、56％和43％（P均＜0．01），并使静息电位（RP）、AP幅值（APA）和0相最大上升速率（Vmax）分别增加30％、30％和45％（P均＜0．01）；高浓度的MT（0．1mmol／L）使正常豚鼠乳头肌的APD20、APD50和APD90分别缩短57％、54％和50％（P均＜0．01），并且RP、APA及Vmax分别下降22％（P＜0．05）、28％（P＜0．01）和29％（P＜0．05），而使缺氧豚鼠乳头肌的APD20、APD50和APD90分别延长92％、78％和50％（P均＜0．01），对RP、APA及Vmax无明显影响。在复氧期间，0．02mmol／L的MT可使自律性的发生率从77．8％降至55．6％（P＜0．05）；而0．1mmol／L的MT则使自律性的发生率从77.8％降至22．2％（P     

New insights on P2X purinoceptors

Significant advances in understanding of P_2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown. Despite these issues, convincing evidence for P_2X receptor heterogeneity, from data with agonists, has recently been reported.A number of new antagonists at P_2X purinoceptors have also recently been described which to some degree appear to be more specific and useful than earlier antagonists like suramin. It is now apparent that suramin is a poor antagonist of ATP in many tissues because it potently inhibits ATPase activity at similar concentrations to those at which it blocks the P_2X purinoceptor.Advances in the use of radiolabelled nucleotides as radioligands for binding studies has allowed the demonstration of P_2X purinoceptors in a variety of tissues throughout the body including the brain. These studies have also provided evidence for receptor heterogeneity. Excitingly, two P_2X purinoceptor genes have been cloned but operational studies suggest that more than two types exist. The cloning studies have also demonstrated a unique structure for the P_2X purinoceptor which differentiates it from all other ligand-gated ion channel receptors. Further studies on P_2X purinoceptor operation and structure are needed to help resolve controversies alluded to regarding the characterization and classification of nucleotide receptors. Hopefully such studies will also lead to a better understanding of the physiological and pathological importance of ATP and its activation of P_2X purinoceptors. This will require the identification of better drug tools, in particular antagonists which may also provide the basis for novel therapeutic agents.     

神经电生理检测对多灶性运动神经病诊断价值的初步研究

目的 探讨神经电生理检查在多灶性运动神经病(MMN)中的诊断价值。方法对16例MMN患者及16名健康对照进行运动神经传导速度和感觉神经传导速度检查，记录刺激引出的复合肌肉动作电位的波幅、波宽、面积、位相和时限，进行对比分析，判定是否有运动神经传导阻滞(CB)或暂时性离散(TD)，并有选择性地进行常规肌电图检查。结果16例患者均可见有一根以上运动神经或至少一根运动神经的一个以上部位出现CB或CD。其中13例双上肢正中神经，尺神经出现CB，3例以正中神经、尺神经的远端出现CB首发，随病情进展出现下肢腓深神经CB。仅有2例感觉神经传导速度稍有减慢，波幅略有降低。16例患者神经受累区域以下所支配肌肉肌电图检查见有神经源性损害。结论MMN是一种以远端神经受累为主的不对称性周围神经病，神经电生理检查对诊断和鉴别诊断．MMN起重要作用，CB是MMN的主要神经电生理表现。     

Action of intravenously administered talipexole on the rat striatal neurons receiving excitatory input from nigral dopamine neurons

Electrophysiological studies using rats anesthetized with chloral hydrate were performed to elucidate whether or not intravenously injected talipexole acted as a D₂ receptor agonist on the striatal neurons in comparison with the action of bromocriptine. The activities of the striatal neurons were extracellularly recorded using a glass microelectrode attached along a seven-barreled micropipette, each barrel of which was filled with talipexole, bromocriptine, SCH23390 (D₁ antagonist), domperidone (D₂ antagonist), glutamate or 2 M NaCl. These drugs were iontophoretically applied to the immediate vicinity of the target neuron being recorded. The effects of talipexole and bromocriptine were examined on the neurons, whose spikes (induced by the stimulation of the substantia nigra pars compacta) were inhibited by the iontophoretic application of domperidone. Iontophoretic application of talipexole or bromocriptine increased spontaneous firing of these neurons and this increase in firing was also inhibited by iontophoretically applied domperidone. In the same neurons, intravenously administered talipexole (0.01, 0.02 and 0.04 mg/kg) dose-dependently increased firing, and this increase was inhibited by microiontophoretically applied domperidone, but not by SCH23390. On the other hand, the intravenous injection of bromocriptine (0.1, 0.2 and 0.4 mg/kg) also increased the firing rate. However, the increase was not dose-dependent and fluctuated; the firing transiently decreased during the increase in firing with intravenously administered bromocriptine. However, the bromocriptine-induced increase in firing was also suppressed by domperidone, and decrease in firing was inhibited by SCH23390. These findings suggest that talipexole acts as a D₂ agonist on the striatal neurons receiving input from substantia nigra pars compacta and increases firing when intravenously applied. However, intravenously administered bromocriptine appears to act as both a D₂ agonist and probably as a D₁ agonist on the striatal neurons to increase and decrease firing, respectively.     

神经干细胞移植防治骨骼肌失神经肌萎缩的电生理研究

目的探讨采用神经干细胞移植的方法防治骨骼肌失神经萎缩的可行性。方法采用机械分离的方法从孕14～16 d的SD孕鼠中获取神经干细胞,并于神经元限定性培养基中进行传代培养,制备神经干细胞单细胞悬液。采用切断右侧胫神经的方法建立腓肠肌失神经支配的动物(SD大鼠)模型。将108只SD大鼠按注射药物的不同随机分为3组,每组36只大鼠。实验组:将神经干细胞悬液注射到切断的胫神经远端。损伤组:注射等量的生理盐水。对照组:注射等量的细胞培养液。术后8、12周采用HRP逆行示踪技术检测失神经骨骼肌重获神经再支配的情况,并应用肌肉电生理方法对重获神经再支配的骨骼肌进行功能评价。结果术后8、12周实验组用电刺激细胞移植部位的腓肠肌,均可引出肌肉收缩活动;且随着时间的延长,单次收缩的波幅、速度,和强直收缩的时间和强直收缩波幅的恢复率均进一步得到改善。对照组和损伤组均未能引出肌肉活动。结论神经干细胞移植能够实现失神经骨骼肌的神经再支配,并且能够与骨骼肌建立起功能性突触连接,有效预防骨骼肌的萎缩。     

腰椎疾患对男性性功能影响的临床观察

目的:探讨腰椎疾患对男性性功能的影响和心理干预治疗的效果.方法:157例伴有性功能障碍的男性腰椎疾患患者分为单纯腰椎疾患组(82例,A组)和继发马尾神经综合征组(75例,B组),治疗前填写国际勃起功能指数评分表(IIEF-5)、艾森克个性问卷(EPQ),同时行球海绵体肌反射(BCR)、坐骨海绵体肌反射(ICR)、阴茎背神经体感诱发电位(SSEP)潜伏期、波幅的检测.A组患者分为对照组和心理干预组;B组患者经临床分为早、中、晚期后再分为对照组和心理干预组.对照组均给予手术治疗.心理干预组除了手术治疗外,同时给予心理干预治疗.治疗后再次采用IIEF-5和BCR、ICR、SSEP检测,并与治疗前进行统计比较.结果:A组患者性功能障碍主要为轻度勃起功能障碍(ED),而B组患者主要为重度ED.A组患者BCR、ICR、SSEP检测结果同正常值相比无显著性差异(P>0.05):心理干预组IIEF-5评分较对照组显著提高(P<0.05).B组患者中,轻度ED患者潜伏期较正常值和A组延长(P<0.05),中度ED和重度ED患者潜伏期延长更加明显(P<0.05);处于临床早期的患者心理干预治疗组性功能的改善情况好于对照组(P<0.05),但是处于临床中、晚期的患者治疗组与对照组的差异不明显(P>0.05).结论:单纯腰椎疾患及临床早期马尾神经综合征患者性功能障碍的发生主要受心理因素的影响,而中晚期马尾神经综合征患者以神经功能损伤为主.心理治疗能够改善单纯腰椎疾患及临床早期马尾综合征患者的性功能,对处于临床中、晚期的马尾神经综合征患者效果不明显.