DO NEURONS FROM RAT NEOSTRIATUM EXPRESS BOTH A TTX-SENSITIVE AND A TTX-INSENSITIVE SLOW NA+ CURRENT
DO NEURONS FROM RAT NEOSTRIATUM EXPRESS BOTH A TTX-SENSITIVE AND A TTX-INSENSITIVE SLOW NA+ CURRENT
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DOI：
10.1152/jn.1995.74.3.934
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发表时间：
1995-09-01
影响因子：
2.5
通讯作者：
ALZHEIMER, C
中科院分区：
文献类型：
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作者：
CHAO, TI;ALZHEIMER, C
1.采用全细胞膜片钳技术，研究了急性分离的大鼠新纹状体神经元对河豚毒素(TTX)敏感的持续钠电流和TTX不敏感的慢钠电流的特性。TTX敏感的持续钠电流(I-NAP)在-60 mV时被激活，在-40 mV时达到-40~-120 pA的峰值。如缓慢的去极化电压斜坡所示，I-NAP的激活不需要快速失活的Na+电流的预先激活。I-NAP的电流-电压(I-V)关系在经过-40 mV附近的峰值后出现了意外的拐点。在-40 mV和-10 mV之间，i-NAP随去极化而下降的速度比在更多去极化时更快。相应的电导(G(Nap))在-40 mV时达到峰值，在电位为-10 mV左右时下降到一个较小的极限值。这一行为与认为I-NAP仅由钟形窗口电导产生的观点不一致，该钟形窗口电导是由窄电压范围内快Na+电流的稳态激活和失活曲线重叠产生的，也不符合I-NAP是由独立于快Na+电流的单一均匀电导产生的概念。除I-NAP外，当内溶液中省略一价小阳离子时，还诱发第二慢内向电流(I-S)。I-NAP和I-S既存在于类似中棘神经元的细胞中，也存在于类似于棘间神经元的细胞中。I-S对河豚毒素(1.2mM)和钙通道阻滞剂镉不敏感。I-S被激活到-45 mV左右，最大幅度达到-200~-500 pA，接近0 mV。这种电流的动力学和药理学特征与最近在相同制备方法中描述的慢钠电流(I-NaS)几乎相同。令我们惊讶的是，当在具有生理阳离子浓度的溶液中进行全细胞记录时，或者当内液中存在高Cs+时，I-S而不是I-NAP消失。我们的数据为持续的、对TTX敏感的Na+电流提供了证据，其特征表明它应该影响阈值下电压区域新纹状体神经元的内在兴奋性。然而，当生理阳离子梯度建立时，我们未能识别出TTX不敏感的慢钠电流。
1. The properties of a tetrodotoxin (TTX)-sensitive, persistent Na+ current and a purported TTX-insensitive slow Na+ current were studied in acutely isolated neurons from rat neostriatum with the use of the whole cell configuration of the patch-clamp technique.2. A TTX-sensitive, persistent Na+ current (I-NaP) was activated positive to -60 mV and reached a peak amplitude of -40 to -120 pA at about -40 mV. As indicated by slow depolarizing voltage ramps, activation of I-NaP did not require preceding activation of the fast, rapidly inactivating Na+ current.3. The current-voltage (I-V) relationship of I-NaP displayed an unexpected inflection after passing through its peak value near -40 mV. Between -40 and -10 mV, I-NaP declined more rapidly with depolarization than it did at more depolarized potentials. The corresponding conductance (G(NaP)) peaked at -40 mV and declined to a smaller limiting value at potentials positive to about -10 mV.4. This behavior is not consistent with the notion that I-NaP arises solely from a bell-shaped window conductance that results from the overlapping steady-state activation and inactivation curves of the fast Na+ current in a narrow voltage range, nor with the notion that I-NaP is generated by a single uniform conductance independent of the fast Na+ current.5. In addition to I-NaP a second slow inward current (I-s) was evoked when small monovalent cations were omitted from the internal solution. I-NaP and I-s were present both in cells resembling medium spiny neurons and in cells resembling aspiny interneurons.6. I-s was insensitive to TTX (1.2 mu M) and the Ca2+ channel blocker, cadmium. I-s was activated positive to about -45 mV and attained a maximum amplitude of -200 to -500 pA close to 0 mV. The kinetic and pharmacological profile of this current was almost identical to that of a slow Na+ current (I-NaS) recently described in the same preparation.7. To our surprise, I-s, but not I-NaP, disappeared when whole cell recordings were performed in solutions with physiological cation concentrations, or when high Cs+ was present in the internal solution.8. Our data provide evidence for a persistent, TTX-sensitive Na+ current, the features of which suggest that it should influence the intrinsic excitability of neostriatal neurons in the subthreshold voltage region. We failed, however, to identify a TTX-insensitive slow Na+ current when physiological cation gradients were established.