生长抑素调节疑核神经兴奋性氨基酸受体介导的兴奋

在含有孤束中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束－疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ－ｍｅｔｈｙｌ－Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ－２－ａｍｉｎｏ－７－ｐｈｏｓｐｈｏｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ－７）使疑核神经元     

生长抑素调节疑核神经元兴奋性氨基酸受体介导的兴奋

在含有孤束核中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束─疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ—ｍｅｔｈｙｌ—Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ—２—ａｍｉｎｏ—７一ｐｂｏｓｐｈｏ－ｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ─７）使疑核神经元兴奋性突触后电位（ＥＰＳＰ）幅度降低，而ＳＳＴ可翻转ＡＰ—７的抑制效应；对ｎｏｎ—ＮＭＤＡ介导的疑核神经元膜去极化，ｃｙｓｔｅａｍｉｎｅ亦对其有明显抑制作用；甘氨酸（ｇｌｙｃｉｎｅ）可阻断ＳＳＴ易化疑核神经元的去极化作用。这些结果表明，ＳＳＴ对疑核神经元兴富性氨基酸（ＥＡＡ）受体介导的兴奋起重要的调节作用。     

一氧化氮与帕金森病小鼠模型神经损害的研究

目的　研究一氧化氮（ＮＯ） 在帕金森病（ＰＤ）小鼠模型神经损害中的作用。方法　用比色分析、高效液相色谱电化学及免疫组化法检测１甲基４苯基四氢吡啶（ＭＰＴＰ）和７硝基吲唑（７ＮＩ）对Ｃ５７ＢＬ小鼠纹状体一氧化氮合酶（ＮＯＳ） 活性,多巴胺（ＤＡ）、二羟基苯乙酸（ＤＯＰＡＣ）、高香草酸（ＨＶＡ） 水平和酪氨酸羟化酶（ＴＨ） 免疫阳性神经纤维的影响。结果　注射ＭＰＴＰ后Ｃ５７ＢＬ小鼠纹状体ＮＯＳ活性增加,７ＮＩ能明显抑制ＭＰＴＰ引起的ＮＯＳ活性的升高（ 分别为０ ．９３ ±０．２４ 和０．５４ ±０．１６,ｎｍｏｌ·ｍｉｎ－１·ｇ－１ 组织,Ｐ＜０．０１） 。７ＮＩ能明显减轻ＭＰＴＰ引起的Ｃ５７ＢＬ小鼠纹状体ＤＡ（ 分别为０ ．８ ±０ ．２ 和６．８±０．５,μｇ／ｇ 组织,Ｐ＜０．０１） 、ＤＰＯＡＣ（ 分别为０．３ ±０．１ 和０ ．９ ±０ ．３ ,μｇ／ｇ 组织,Ｐ＜ ０ ．０１）、ＨＶＡ（分别为０．４±０．２ 和０．９ ±０ ．２,μｇ／ｇ 湿组织,Ｐ＜ ０．０１） 的降低及ＴＨ 阳性神经纤维损害。结论神经元来源的ＮＯ 参与了ＭＰＴＰ的毒性机制,神经元型ＮＯＳ抑制剂可能有益于ＰＤ的治疗。     

新生期注射谷氨酸单钠对刺激下丘脑弓状核镇痛作用的影响

下丘脑弓状核（ＡＲＣ）是脑内β－内啡肽（β－ＥＮＤ）能神经元胞体集中的一个主要核团。新生期注射谷氨酸单钠（ＭＳＧ）能选择性地损毁ＡＲＣ中的神经元胞体而不累及路过纤维，是研究ＡＲＣ中神经元生理功能的一个良好模型。本实验利用这个实验模型研究刺激ＡＲＣ的镇痛效应。结果发现在这种ＭＳＧ处理的大鼠，刺激ＡＲＣ不再出现明显的镇痛效应（用电刺激鼠尾－嘶叫法测定）。这时脑室内注射β－ＥＮＤ（５μｇ／１０μｌ）能使刺激ＡＲＣ的镇痛效应恢复；若脑室注射多巴胺（ＤＡ，５μｇ／１０μｌ）不仅没有恢复作用，反而能削弱正常大鼠刺激ＡＲＣ的镇痛效应。实验结果提示，经ＭＳＧ处理的大鼠之所以不出现明显的镇痛效应，可能是由于ＡＲＣ中丧失了β－ＥＮＤ能神经元的结果，ＤＡ能神经元在其中不起重要作用。     

糖皮质激素对大鼠大脑皮层突触体高亲和摄取L—谷氨酸的快速,非基因组效应

本研究采用大鼠大脑皮层突触体，观察糖皮质激素（ＧＣ）对于Ｎａ＋依赖高亲和摄取３Ｈ－Ｌ谷氨酸（孵育４ｍｉｎ）的影响。发现ＧＣ包括皮质酮硫酸盐（Ｂ－ＳＯ４）、氢化可的松琥珀酸盐（Ｆ－ｓｕｃ）、地塞米松磷酸盐（ＤＥＸ－ＰＯ４）及皮质酮（Ｂ）均促进突触体摄取谷氨酸，且呈一定浓度依赖性。Ｂ－ＳＯ４１０－５ｍｏｌ／Ｌ时，谷氨酸摄取较对照组增加２５．６％，Ｂ－ＳＯ４、Ｆ－Ｓｕｃ及Ｂ最低有效剂量均为１０－７ｍｏｌ／Ｌ，ＤＥＸ－ＰＯ４最低有效剂量为１０－６ｍｏｌ／Ｌ。孵育２ｍｉｎ后即见Ｂ－ＳＯ４（１０－６ｍｏｌ／Ｌ）促进突触体摄取谷氨酸，孵育４ｍｉｎ后Ｂ－ＳＯ４的作用达高峰。１０－６ｍｏｌ／Ｌ睾酮及孕酮也有促进摄取谷氨酸的作用，而去氧皮质酮及１７β－雌二醇硫酸盐对突触体摄取谷氨酸没有显著影响，ＧＣ的作用有一定甾体特异性。ＧＣ胞内受体阻断剂ＲＵ４８６本身对谷氨酸摄取没有影响，但可部份阻断Ｂ的促进作用。由于已从神经元上离断下来的突触体不再受基因组机制影响，本实验中ＧＣ快速促进突触体摄取谷氨酸是非基因组机制介导的，其详细机制及潜在生理意义有待进一步探讨。     

重症肌无力患者HLA－DRB_1等位基因分析

作者应用ＰＣＲ－ＳＳＰ方法，对３４例重症肌无力（ＭＧ）患者和８６名健康汉人ＨＬＡ－ＤＲＢ１等位基因进行分析、研究，结果发现，ＭＧ病人组ＭＲＢ１区域内０９０１、１３０１两对等位基因的频率明显高于对照组（ＲＲ分别为１６．９４４和５．５１２，Ｐ均＜０．０１）。其中８例伴有胸腺瘤的ＭＧ患者除０９０１、１３０１两对等位基因频率增高外，０４０１基因频率亦明显高于正常对照组（ＲＲ分别为３９．５０３、４．９８０和４．０００．Ｐ均＜０．０１）。作者认为，ＭＧ发病可能与ＨＬＡ－ＤＲＢ１区域内０９０１、１３０１和０４０１三对等住基因相关联。     

重症肌无力病人血清中IgM型乙酰胆碱受体,突触前膜抗体检测及 …

应用ＡＢＣ－ＥＬＩＳＡ法检测了９６例重症肌无力（ＭＧ）病人血清中ＩｇＭ－ＡｃｈＲ、Ｐｓｍａｂ。发现ＭＧ组中，有１８例（１８．７％）ＩｇＭ－ＡｃｈＲａｂ阳性；１０例（１０．４％）ＩｇＭ－Ｐｓｍａｂ阳性。ＩｇＭ－Ｐｓｍａｂ阳性频见于病程〈２年的ＭＧ病人；而与ＭＧ组病人的年龄和临床分型均无显著的相关性（Ｐ〉０．０５）。结果提示ＩｇＭ型抗体也与ＩｇＭ型抗体共同参与了ＭＧ的发病机制，且提示有神经肌肉接头突触     

类鸦片受体δ2介导的免疫细胞激活作用

将人粒细胞和Ｍｙｔｉｌｕｓｅｄｕｌｉｓ免疫细胞分别与不同浓度的类鸦片肽ＤＡＭＡ（１０（－１３）～１０（－１０）ｍｏｌ／Ｌ）或δ拮抗剂在３７和２３℃保温１０～２０ｍｉｎ，用计算机显微图像分析法分析两种细胞的活化情况。结果显示细胞免疫活性随ＤＡＭＡ浓度增加而提高，细胞发生阿米巴样变形或变长（形状因子小于０．５）。当加入δ拮抗剂ｎａｌｔｒｉｎｄｏｌｅ（１０（－１０）ｍｏｌ／Ｌ）时，ＤＡＭＡ对以上两种细胞的免疫激活作用均受到显著抑制（Ｐ＜０．０５），说明该类鸦片肽受体能被低浓度ｎａｌｔｒｉｎｄｏｌｅ封闭；然而，同样浓度的另一种δ拮抗剂钠洛酮却没有这种封闭作用，提示ＤＡＭＡ通过δ_２受体的介导发挥对免疫细胞的激活作用。     

P物质和谷氨酸介导辣椒素引起的脊髓γ—氨基丁酸的释放

以前的实验证明辣椒素急性处理外周神经可导致初级传入末梢大量释放Ｐ物质，同时也观察到脊髓背角浅层ＧＡＢＡ的排空。本研究的目的在于探讨外周施加辣椒素激活背角ＧＡＢＡ能神经元，是否与初级传入末梢释放的递质有关。结果表明，外周胫神经辣椒素处理３０分钟即可引起的同侧背角浅层ＧＡＢＡ免疫反应产物（ＧＡＢＡ—ＩＲ）的明显减少，予先用ＮＫ—１受体桔抗剂Ｓｐａｎｔｉｄｅ（５０ｎＭ）或ＮＭＤＡ受体拮抗剂ＡＰＶ（１００μＭ）灌流脊髓腰膨大表面，可部分阻断辣椒素引起的ＧＡＢＡ—ＩＲ密度和ＧＡＢＡ—ＩＲ阳性神经元数目的减少，使ＧＡＢＡ—ＩＲ有不同程度的恢复。本文讨论了初级传入末梢释放的Ｐ物质和兴奋性氨基酸与ＧＡＢＡ能神经元在脊髓痛觉信息调制中的作用。     

垂体腺苷酸环化酶激活肽减轻一氧化氮介导的谷氨酸神经毒作用

研究垂体腺苷酸环化酶激活肽是和用于一氧化氮代谢途径,减轻谷氨酸神经毒作用。取新生ＳＤ大鼠海马,用Ｂ２７无血清培养基培养神经元;重氮,化反应法测定ＮＯ浓度,则定神经元存活率,ＰＡＣＡＰ能减少谷氨酸引起的海马神经元死亡;谷氨于剂量依赖性地增加海马神经元培养液中ＮＯ的含量,ＰＡＣＡＰ能不同程度地减少ＮＯ的含量,分别给予２ｍｍｏｌ／Ｌ Ｌ－Ａｇ,１００μｍｏｌ／Ｌ ＳＮＰ和２００μｍｏｌ／Ｌ ＳＡＮＰ处理     

Fibrotic scar model and TGF‐β1 differently modulate action potential firing and voltage‐dependent ion currents in hippocampal neurons in primary culture

Traumatic injury of the central nervous system is accompanied by various functional and morphological changes. Animal models of traumatic brain injury are commonly used to investigate changes in behaviour, morphology, in the expression of various proteins around the site of the injury, or the expression of diagnostically important biomarkers. Excitability of a single neuron at, or close to, the site of injury was rarely investigated. Several in vitro models were developed which allow such investigation. In the present work, we employed a fibrotic scar model according to Kimura‐Kuroda and coauthors to analyse altered excitability of rat hippocampal neurons under the conditions mimicking traumatic brain injury. Hippocampal neurons from newborn rats were cultured either on a fibrotic scar model or in the presence of TGF‐β1, a cytokine secreted at a brain injury site that may have both neuroprotective and neurodegenerative function. Fibrotic scar facilitated ability of neonatal hippocampal neurons to fire action potential series by increasing the density of voltage activated sodium and potassium currents. Chondroitin sulphate proteoglycans played substantial role in these effects, as proven by their full reversion after administration of Chondroitinase ABC. In contrast, TGF‐β1 did not contribute to them. An application of TGF‐β1 itself attenuated generation of action potentials, inhibited sodium current and potentiated potassium currents. Main alteration of electrophysiological parameters of neonatal hippocampal neurons caused by a fibrotic scar model is enhanced excitability. TGF‐β1 may have predominantly neuroprotective role in injured rat hippocampus.     

Voltage-dependent ionic channels in differentiating neural precursor cells collected from adult mouse brains six hours post-mortem

A novel type of adult neural precursor cells (NPCs) has been isolated from the subventricular zone of the mouse 6 hr after animal death (T6-NPCs). This condition is supposed to select hypoxia-resistant cells of scientific and clinical interest. Ionic channels are ultimately the expression of the functional maturation of neurons, so the aim of this research was to characterize the pattern of the main voltage-dependent ionic channels in T6-NPCs differentiating to a neuronal phenotype, comparing it with NPCs isolated soon after death (T0-NPCs). T6- and T0-NPCs grow in medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Differentiation was performed in small wells without the addition of growth factors, in the presence of adhesion molecules, fetal bovine serum, and leukemia inhibitory factor. Ionic currents, recorded by means of whole-cell patch-clamp, namely, I(Ca2+) HVA, both L- and non-L-type, I(K+) delayed rectifying, I(K+) inward rectifier, transient I(K+A) , and TTX-sensitive I(Na+) have been found, although Na(+) currents were found in only a small percentage of cells and after the fifth week of differentiation. No significant differences in current types, density, orcell capacitance were observed between T6-NPCs and T0-NPCs. The sequence in which the markers appear in new neural cells is not necessarily a fixed program, but the discrepancies in morphological, biochemical, and electrophysiological maturation of mouse NPCs to neurons, possibly different in vivo, suggest that the various steps of the differentiation are independently regulated. Therefore, in addition to morphological and biochemical data, functional tests should be considered for characterizing the maturation of neurons.     

The voltage‐dependent conductances of rat neocortical layer I neurons

Whole cell patch-clamp techniques were used to study voltage-dependent sodium (Na⁺), calcium (Ca²⁺), and potassium (K⁺) conductances in acutely isolated neurons from cortical layer I of adult rats. Layer I cells were identified by means of γ-aminobutyric acid (GABA) immunocytochemistry. Positive stainings for the Ca²⁺-binding protein calretinin in a subset of cells, indicated the presence of Cajal–Retzius (C-R) cells. All investigated cells displayed a rather homogeneous profile of voltage-dependent membrane currents. A fast Na⁺ current activated at about −45 mV, was half-maximal steady-state inactivated at −66.6 mV, and recovery from inactivation followed a two-exponential process (τ₁ = 8.4 ms and τ₂ = 858.8 ms). Na⁺ currents declined rapidly with two voltage-dependent time constants, reaching baseline current after some tens of milliseconds. In a subset of cells (< 50%) a constant current level of < 65 pA remained at the end of a 90 ms step. A transient outward current (I_fast) activated ≈–40 mV, declined rapidly with a voltage-insensitive time constant (τ≈ 350 ms) and was relatively insensitive to tetraethylammonium (TEA, 20 mm ). I_fast was separated into two components based on their sensitivity to 4-aminopyridine (4-AP): one was blocked by low concentrations (40 μm ) and a second by high concentrations (6 mm ). After elimination of I_fast by a conditioning prepulse (50 ms to −50 mV), a slow K⁺ current (I_KV) could be studied in isolation. I_KV was only moderately affected by 4-AP (6 mm ), while TEA (20 mm ) blocked most (> 80%) of the current. I_KV activated at about −40 mV, declined monoexponentially in a voltage-dependent manner (τ≈ 850 ms at −30 mV), and revealed an incomplete steady-state inactivation. In addition to I_fast and I_KV, indications of a Ca²⁺-dependent outward current component were found. When Na⁺ currents, I_fast, and I_KV were blocked by tetrodotoxin (TTX, 1 μm ), 4-AP (6 mm ) and TEA (20 mm ) an inward current carried by Ca²⁺ was found. Ca²⁺ currents activated at depolarized potentials at about −30 mV, were completely blocked by 50 μm cadmium (Cd²⁺), were sensitive to verapamil (≈ 40% block by 10 μm ), and were not affected by nickel (50 μm ). During current clamp recordings, isolated layer I neurons displayed fast spiking behaviour with short action potentials (≈ 2 ms, measured at half maximal amplitude) of relative small amplitude (≈ 83 mV, measured from the action potential threshold).     

Developmental expression of Na+ currents in mouse Purkinje neurons

As Purkinje neurons mature during postnatal development, they change from electrically quiescent to active and exhibit high frequency spontaneous action potentials. This change in electrical activity is determined by both alteration in ion channel expression and the acquisition of synaptic input. To gain a better understanding of the development the intrinsic electrical properties of these neurons, acutely isolated Purkinje neurons from mice aged postnatal day 4 (P4) to P18 were examined. This included recording action potential frequency, threshold, height and slope, and input resistance and capacitance. Changes in a number of these properties were observed, suggesting significant changes in voltage-gated Na(+) currents. Because voltage-gated Na(+) currents, including the transient, resurgent and persistent currents, are known to play important roles in generating spontaneous action potentials, the developmental changes in these currents were examined. A large increase in the density of transient current, resurgent current and persistent current was observed at times corresponding with changes in action potential properties. Interestingly, the developmental up-regulation of the persistent current and resurgent current occurred at rate which was faster than the up-regulation of the transient current. Moreover, the relative amplitudes of the persistent and resurgent currents increased in parallel, suggesting that they share a common basis. The data indicate that developmental up-regulation of Na(+) currents plays a key role in the acquisition of Purkinje neuron excitability.     

Ionic basis of the membrane potential responses of rat dorsal vagal motoneurones to HEPES buffer

The effects of 10 mM HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid) buffered artificial cerebrospinal fluid (aCSF) on membrane potential and the action potential were studied in 93 dorsal vagal motoneurones (DVMs) using an in vitro slice preparation of the rat medulla. Changing from bicarbonate/CO₂ aCSF to HEPES aCSF resulted in a depolarisation of 6.0 ± 0.6 V and an increase in input resistance (R_In; N = 61). In the presence of 5 mM 4-AP, HEPES either had little effect (n = 9) or hyperpolarised the membrane (n = 10). Mn²⁺ (3 mM) or Ni²⁺ (200 μm) abolished the hyperpolarisation and its associated increase in R_In. In voltage-clamp studies 5 mM 4-AP eliminated a transient outward current and Ni²⁺ blocked an inactivating inward current. It is concluded that HEPES buffer reduces the contribution of the A current to resting membrane potential and also reduces a Ni²⁺-sensitive transient I_Ca.     

Delayed potassium current and non-specific outward current in pyramidal neurones acutely dissociated from rat hippocampus

The electrical property of delayed K+ currents (IKD) was studied in pyramidal neurones freshly isolated from the rat hippocampal CA1 region. The IKD was separated pharmacologically from other membrane currents. Activation and inactivation processes of the IKD were highly voltage-dependent in the potential range between -30 and +20 mV. The steady-state inactivation of IKD was observed at -100 mV or more positive potentials. The potential for half steady-state inactivation was -65 mV. The IKD was fully inactivated around -20 mV. Reactivation of IKD consisted of two exponential components. After pharmacological suppression of IKD, the small amount of residual voltage-dependent outward current (one-fifteenth to one-twentieth of IKD amplitude) was observed. The current kinetics was similar to that of IKD and greatly reduced by substitution of internal K+ with N-methyl-D-glucamine+. It was concluded that the properties of IKD was basically similar to those of IKD in other excitable tissues and that the residual current might be non-specific outward current.     

Effects of insulin-like growth factor 1 on voltage-gated ion channels in cultured rat hippocampal neurons

Insulin-like growth factor 1 (IGF-1) has important functions in the brain, including metabolic, neurotrophic, neuromodulatory, and neuroendocrine actions, and it is also prevents amyloid beta-induced death of hippocampal neurons. However, its functions on the voltage-gated ion channels in hippocampus remain uncertain. In the present study, we investigated the effects of IGF-1 on voltage-gated potassium, sodium, and calcium channels in the cultured rat hippocampal neurons using the whole-cell patch clamp recordings. Following incubation with different doses of IGF-1 for 24 h, a block of the peak transient A-type K+ currents amplitude (IC50: 4.425 ng/ml, Hill coefficient: 0.621) was observed. In addition, after the application of IGF-1, the amplitude of high-voltage activated Ca2+ currents significantly increased but activation kinetics did not significantly alter (V1/2: -33.45 +/- 1.32 mV, k = 6.16 +/- 1.05) compared to control conditions (V1/2: -33.19 +/- 2.28 mV, k = 7.26 +/- 1.71). However, the amplitude of Na+, K+, and low-voltage activated Ca2+ currents was not affected by the application of IGF-1. These data suggest that IGF-1 inhibits transient A-type K+ currents and enhances high-voltage-activated Ca2+ currents, but has no effects on Na+ and low-voltage-activated Ca2+ currents.     

双分离法记录Wistar大鼠神经元的全细胞电流

背景：细胞培养与通道电流记录是全细胞膜片钳实验的主要难点。 目的：介绍一种简单可行的降低全细胞膜片钳实验方法，将细胞急性分离与电流的分离技术结合起来，以提高工作效率，缩短实验的时间，从根本上降低膜片钳实验的难度。 方法：SPF级出生4~7 d的wistar大鼠40只，雌雄不限。采用改良的急性分离的方法制备Wistar大鼠脑皮质细胞，将大鼠脑皮质切成400~600 μm厚度的薄片，在人工脑脊液中通混合气静止1 h，并通以氧气。将脑组织块放入含有16 u/mL( type X )和2 u/mL(type XIV) 蛋白水解酶的人工脑脊液中，孵育60 min，清除消化酶。在全细胞电压钳制模式下，保持电位 -80 mV，给予-60 mV到60 mV的去极化脉冲刺激，步阶为+10 mV，刺激波宽160 ms。记录到跨膜总电流，在全细胞电极液里面加入70 mmol/LCsCl，70 mmol/L CsF；在外液中先后加入11 μmol/L 阻断剂河豚毒素、30 mmol/L的氯化四乙胺、1 mmol/L的4-AP。分别记录内向钠电流，瞬时外向钾电流和延迟整流钾电流，结果用clampfit分析处理。主要观察：①细胞的形态学观察。②全细胞电流的记录。③内向钠电流的记录。④外向钾电流的记录。 结果与结论：细胞空间立体结构强，表面光滑，有完整的树突或者轴突，且细胞的活性可以在25 ℃室温下维持8~10 h。在外液中加入1 μmol/L的河豚毒素基本上可以阻断钠电流；30 mmol/L的氯化四乙胺和1 mmol/L的4-AP可以阻断外向钾电流。结果表明，改良的细胞急性分离方法细胞功能完好。通过电流分离技术，不改变细胞外液和电极液，仅需添加特异阻断剂，可记录到内向钠电流，瞬时外向钾电流以及延迟整流钾电流，较之传统方法可显著提高工作效率。     

Membrane Currents Influencing Action Potential Latency in Granule Neurons of the Rat Cochlear Nucleus

Granule cells are the most numerous neurons in the cochlear nucleus, but, because of their small size, little information on their membrane properties and ionic currents is available. We used an in vitro slice preparation of the rat ventral cochlear nucleus to make whole-cell recordings from these cells. Under current clamp, some granule neurons fired spontaneous action potentials and all generated a train of action potentials on depolarization (threshold current, 10–35 pA). Hyperpolarization increased the latency to the first action potential evoked during a subsequent depolarization. We examined which voltage-gated currents might underlie this latency shift. In addition to a fast inward Na⁺ current, depolarization activated two outward potassium currents. A transient current was rapidly inactivated by membrane potentials positive to -60 mV, while a second, more slowly inactivating current was observed following the decay of the transient current. No hyperpolarization-activated conductances were observed in these cells. Modelling of the currents suggests that removal of inactivation on hyperpolarization accounts for the increased action potential latency in granule cells. Such a mechanism could account for the 'pauser'-type firing patterns of the fusiform cells which receive a prominent projection from the granule cells in the dorsal cochlear nucleus.