Evoked postsynaptic potentials of CA1 pyramidal neurons in rat hippocampus were studied during 48h after severe ischemic insult using in vivo intracellular recording and staining techniques. Postischemic CAI neurons displayed one of three distinct response patterns following contralateral commissural stimulation. At early recirculation times (0-12h) approximately 50% of neurons exhibited, in addition to the initial excitatory postsynaptic potential, alate depolarizing postsynaptic potential lasting for more than 100ms. Application of dizocilpine maleate reduced the amplitude of late depolarizing postsynaptic potential by 60% Other CAI neurons recorded in this interval failed to develop late depolarizing postsynaptic potentials but showed a modest blunting of initial excitatory postsynaptic potentials (non-late depolarizing postsynaptic potential neuron). The proportion of recorded neurons with late depolarizing postsynaptic potential characteristics increased to more than 70% during 13-24h after reperfusion. Beyond 24h reperfusion, 20% of CA1 neurons exhibited very small excitatory postsynaptic potentials even with maximal stimulus intensity. The slope of the initial excitatory postsynaptic potentials in late depolarizing postsynaptic potential neurons increased to 150% of control values up to 12h after reperfusion indicating a prolonged enhancement of synaptic transmission. In contrast, the slope of the initial excitatory postsynaptic potentials in non-late depolarizing postsynaptic potential neurons decreased to less than 50% of preischemic values up to 24h after reperfusion indicating a prolonged depression of synaptic transmission. More late depolarizing postsynaptic potential neurons were located in the medial portion of CA1 zone where neurons are more vulnerable to ischemia whereas more non-late depolarizing postsynaptic potential neurons were located in the lateral portion of CA1 zone where neurons are more resistant to ischemia. The result from the present study suggests that late depolarizing postsynaptic potential and small excitatory postsynaptic potential neurons may be irreversibly injured while non-late depolarizing postsynaptic potential neurons may be those that survive the ischemic insult. Alterations of synaptic transmission may be associated with the pathogenesis of postischemic neuronal injury.

We have previously identified three distinct populations of CA1 pyramidal neurons after reperfusion based on differences in synaptic response, and named these late depolarizing postsynaptic potential neurons (enhanced synaptic transmission), non-late depolarizing postsynaptic potential and small excitatory postsynaptic neurons (depressed synaptic transmission). In the present study, spontaneous activity and membrane properties of CA I neurons were examined up to 48 h following-14 min ischemic depolarization using intracellular recording and staining techniques in vivo. In comparison with preis-chemic properties, the spontaneous firing rate and the spontaneous synaptic activity of CA1 neurons decreased significantly during reperfusion; spontaneous synaptic activity ceased completely 36-48h alter reperfusion, except for a low level of activity which persisted in non-late depolarizing postsynaptic potential neurons. Neuronal hyperactivity as indicated by increasing firing rate was never observed in the present study. The membrane input resistance and time constant decreased significantly in late depolariz-ing postsynaptic potential neurons at 24-48h reperfusion. In contrast, similar changes were not observed in non-late depolarizing postsynaptic potential neurons. The rheobase, spike threshold and spike frequency adaptation in late depolarizing postsynaptic potential neurons increased progressively following reperfu-sion. Only a transient increase in rheobase and spike threshold was detected in non-late depolarizing postsynaptic potential neurons and spike frequency adaptation remained unchanged in these neurons. The amplitude of fast afterhy perpolarization increased in all neurons after reperfusion, with the smallest increment in non-late depolarizing postsynaptic potential neurons. Small excitatory postsynaptic potential neurons shared similar changes to those of late depolarizing postsynaptic potential neurons. These results suggest that the enhancement and depression of synaptic transmission following ischemia are probably due to changes in synaptic efficacy rather than changes in intrinsic membrane properties. The neurons with enhanced synaptic transmission following ischemia are probably the degenerating neurons, while the neurons with depressed synaptic transmission may survive the ischemic insult.

短暂脑缺血可对随后的损伤性脑缺血表现出明显的耐受，有研究表明大电导ca2+依赖K+（BKCa）通道活动增强参与了缺血性脑损伤，采用膜片钳的内面向外式，观察了3min短暂脑缺血后6h、24h以及48h大鼠海马cAl区锥体细胞上BKca通道活动的动态变化，短暂脑缺血后BKca通道的单通道电导和翻转电位均未见明显变化，但通道的开放概率则在缺血预处理后的前24h内显著降低，通道动力学分析显示通道关闭时间变长是短暂脑缺血后通道活动降低的主要原因，因为通道的开放时间未发生明显变化，结果提示短暂脑缺血所致的BKca通道活动降低可能与缺血耐受的产生有关.

Gao, T. M., E. M. Howard, and Z. C. Xu. Transient neurophysio-logical changes in CA3 neurons and dentate granule ceils after severe forebrain ischemia in vivo. J. Neurophysiol. 80: 2860-2869, 1998. The spontaneous activities, evoked synaptic responses, and membrane properties of CA3 pyramidal neurons and dentate granule cells in rat hippocampus were compared before ischemia and s7 days after reperfusion with intracellular recording and staining techniques in vivo. A four-vessel occlusion method was used to induce ～14 min of ischemic depolarization. No significant change in spontaneous firing rate was observed in both cell types after reperfusion. The amplitude and slope of excitatory postsynap-tic potentials (EPSPs) in CA3 neurons decreased to 50% of control values during the first 12h reperfusion and returned to preischemic levels 24h after reperfusion. The amplitude and slope of EPSPs in granule cells slightly decreased 24-36 h after reperfusion. The amplitude of inhibitory postsynaptic potentials in CA3 neurons transiently increased 24h after reperfusion, whereas that in granule cells showed a transient decrease 24-36 h after reperfusion. The duration of spike width of CA3 and granule cells became longer than that of control values during the first 12h reperfusion. The spike threshold of both cell types significantly increased 24-36h after reperfusion, whereas the frequency of repetitive firing evoked by depolarizing current pulse was decreased during this period. No significant change in rheobase and input resistance was observed in CA3 neurons. A transient increase in rheobase and a transient decrease in input resistance were detected in granule cells 24 36h after reperfusion. The amplitude of fast afterhyperpolarization in both cell types increased for 2 days after ischemia and returned to normal values 7 days after reperfusion. The results from this study indicate that the neuronal excitability and synaptic transmission in CA3 and granule cells are transiently suppressed after severe forebrain ischemia. The depression of synaptic transmission and neuronal excitability may provide protection for neurons after isch-emic insult.

It has been reported previously that the neuronal excitability persistently suppresses and the amplitude of fast afterhyperpolarization (fAHP) increases in CAI pyramidal cells of rat hippocampus following transient forebrain ischemia. To understand the conductance mechanisms underlying these post-ischemic electrophysiological alterations, we compared differences in activities of large conductance Ca2+-activated potassium (BKca) channels in CA1 pyramidal cells acutely dissociated from hippocampus before and after ischemia by using inside-out configuration of patch clamp techniques. (1) The unitary conductance of BKc. channels in post-iscfiemic neurons (295pS) was higher than that in control neurons (245pS) in symmetrical 140/140mM K+ in inside-out patch; (2) the membrane depolarization for an e-fold increase in open probability (P) showed no significant differences between two groups while the membrane potential required to produce one-half of the maximum Po was more negative after ischemia, indicating no obvious changes in channel voltage dependence; (3) the [Ca2+] required to half activate BKca, channels was only 1uM in post-ischemic whereas 2 IxM in control neurons, indicating an increase in [Ca2+], sensitivity after ischemia; and (4) BKca channels had a longer open time and a shorter closed time after ischemia without significant differences in open frequency as compared to control. The present results indicate that enhanced activity of BKc. channels in CAI pyramidal neurons after ischemia may partially contribute to the post-ischemic decrease in neuronal excitability and increase in fAHR.