SYNAPTICALLY TRIGGERED ACTION-POTENTIALS BEGIN AS A DEPOLARIZING RAMP IN RAT HIPPOCAMPAL-NEURONS INVITRO
SYNAPTICALLY TRIGGERED ACTION-POTENTIALS BEGIN AS A DEPOLARIZING RAMP IN RAT HIPPOCAMPAL-NEURONS INVITRO
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DOI：
10.1113/jphysiol.1992.sp019250
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发表时间：
1992-07-01
影响因子：
5.5
通讯作者：
ANDERSEN, P
中科院分区：
文献类型：
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作者：
HU, GY;HVALBY, O;ANDERSEN, P
1. 在离体大鼠海马CA1锥体细胞的阈上突触激活过程中，动作电位以缓慢的去极化斜坡开始，叠加在基础EPSP上，形成动作电位的一个组成部分。我们称之为突触前电位（SyPP）。为了检查SyPP，需要一个减去基础EPSP的程序。由于动作电位仅由大于平均振幅的EPSP子集引起，因此减去平均阈下EPSP不会得到有效的结果。相反，从亚阈值EPSP组合中选择要减去的EPSP，使其振幅与产生尖峰的EPSP的初始部分相匹配。几乎所有的动作电位都是从SyPP开始的。使用匹配的阈下epsp均值的1 sd的振幅标准，从随机选择的15个细胞中，刚刚超过阈的EPSPs给出了72- 100%的动作电位。以2 sd为标准，发生频率范围为36% ~ 100%。当刺激强度恒定时，脉冲潜伏期有一定的可变性。较短的潜伏期峰值比较晚的潜伏期峰值更陡峭，但SyPP更小，这表明SyPP的斜率影响了细胞放电的时间。相对于大振幅动作电位，SyPP更小、更慢，其拟合曲线呈指数上升。其振幅为1 ~ 6 mV，时间常数为1 ~ 5 ms，比动作电位上冲慢10 ~ 50倍。适当定时的超极化电流脉冲可以阻断大振幅动作电位，从而揭开SyPP作为初始去极化斜坡的面纱。SyPP对细胞内注射利多卡因衍生物QX-314比大振幅动作电位更敏感。在使用的浓度（10或30毫米）下，在大振幅动作电位中未观察到可检测的变化。滴注特异性n -甲基- d -天冬氨酸受体拮抗剂dl -2-氨基-5-磷酸戊酸（1 mM）可降低EPSP和放电概率，但未改变sypp。SyPP的振幅和时间过程取决于细胞被激活时的膜电位。去极化增强和延长了SyPP，而超极化则相反。在一定程度上，去极化引起的振幅增加可归因于膜调节。反节律诱发的动作电位从不以前电位开始。在体细胞中注入一个与阈上EPSPs相似的上升相的去极化电流脉冲（5ms），产生了没有初始预电位的动作电位。然而，较长的去极化脉冲会引起从前电位开始的动作电位。刚过阈值的近端输入和远端输入在根尖树突中引起的SyPPs几乎相同。结果表明，CA1锥体细胞的突触触发动作电位有两个阶段，即缓慢的初始预电位和快速的大振幅动作电位，这些动作电位对QX-314有差异敏感。
1. During just-suprathreshold synaptic activation of CA1 pyramidal cells in rat hippocampal slices in vitro the action potential begins as a slow depolarizing ramp, superimposed on the underlying EPSP and forming an integral part of the action potential. We call this ramp a synaptic prepotential (SyPP).2. In order to examine the SyPP, a procedure for subtraction of the underlying EPSP was necessary. Because action potentials were only elicited by a subset of EPSPs with larger than average amplitude, a subtraction of the mean subthreshold EPSP would not give valid results. Instead, an EPSP to be subtracted was selected from an assemblage of subthreshold EPSPs, so that its amplitude matched the initial part of the spike-generating EPSP.3. Virtually all action potentials started with a SyPP. Using an amplitude criterion of 1 S.D. of the mean of the matching subthreshold EPSPs, just-suprathreshold EPSPs gave prepotentials in 72-100 % of all action potentials from fifteen randomly selected cells. With a criterion of 2 S.D.S, the frequency of occurrence ranged from 36 to 100 %.4. With a constant stimulus strength, there was a certain variability of the spike latencies. Shorter latency spikes had steeper, but smaller SyPPs than later spikes, suggesting that the slope of SyPP influenced the timing of the cell discharge.5. The SyPP was best fitted by a single, exponentially rising curve, and was both smaller and slower than the large amplitude action potential. lts amplitude was 1-6 mV and the time constant 1-5 ms, which was 10-50 times slower than that of the upstroke of the action potential.6. A properly timed hyperpolarizing current pulse could block the large amplitude action potential, thereby unmasking the SyPP as an initial depolarizing ramp.7. The SyPP was more sensitive than the large amplitude action potential to intracellular injection of QX-314, a lidocaine derivative. At the concentrations used (10 or 30 mM) no detectable changes were seen in the large amplitude action potential.8. Droplet application of a specific N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonovaleric acid (1 mM), reduced both the EPSP and the firing probability, but did not change the SyPP.9. The SyPP amplitude and time course depended upon the membrane potential at which the cell was activated. Depolarization enhanced and prolonged the SyPP, while hyperpolarization gave opposite effects. In part, the depolarization-induced amplitude increase could be attributed to membrane accommodation.10. Antidromically evoked action potentials never started with a prepotential. Injection of a depolarizing current pulse (5 ms) in the soma with a rising phase similar to that of the suprathreshold EPSPs gave action potentials without an initial prepotential. Longer depolarizing pulses, however, elicited action potentials starting with a prepotential.11. The SyPPs elicited by just-suprathreshold proximal and distal inputs in the apical dendrites were nearly identical.12. The results suggest that synaptically triggered action potentials in CA1 pyramidal cells have two phases: a slow initial prepotential followed by a fast, large amplitude action potential which are differentially sensitive to QX-314.