为探讨钾通道参与神经元凋亡的可能机制，在星形孢菌素（STS）诱导的培养海马神经元凋亡模型上，研究了凋亡时神经细胞容积的动态变化及钾通道在其中的作用。实验结果显示，钾通道阻断剂四乙铵或升高细胞外K+均能够明显抑制STS诱导的神经元凋亡，并且大电导钙激活钾通道（BK）选择性阻断剂iberiotoxin和paxilline具有同样程度的抗细胞凋亡作用，表明钾通道（可能主要是BK通道）参与了STS诱导的培养海马神经元凋亡，在STS诱导神经元凋亡的早期就出现了细胞容积的显著减少，而钾通道阻断剂或升高细胞外K+均可阻断该细胞容积减少，研究结果提示细胞内钾离子的外流可能参与了凋亡性细胞容积减少，这也可能是钾通道介导细胞凋亡的重要机制之一。

Neurophysiological changes of hippocampal neurons were compared before and after transient forebrain ischemia using intracellu-lar recording and staining techniques in vivo. Ischemic depolarization (ID) was used as an indication of severe ischemia. Under halo-thane anesthesia, approximately 13 rain of ID consistently produced severe neuronal dam-age in the CA1 region of rat hippocampus, while CA3 pyramidal neurons and dentate granule cells remained intact. After such se-vere ischemia, approximately 60% of the CA1 neurons exhibited a synaptic potentia-tion. The excitability of these neurons pro-gressively decreased following reperfusion. Approximately 30% of the CA1 neurons showed a synaptic depression following ischemia. The excitability of these neurons transiently decreased following reperfusion. After ischemia of the same severity, both synaptic transmission and excitability of CA3 and granule cells transiently depressed. These data suggest that ischemia-induced synaptic potentiation may be associated with the pathogenesis of neuronal damage fol-lowing ischemia, and that the synaptic de-pression may have protective effects on hip-pocampal neurons after ischemic insult.

It has been recently reported that potassium channel increases activities in CA1 pyramidal neurons of rat hippocampus following transient forebrain ischemia. To understand the role of the enhanced potassium current in the pathogenesis of neuronal damage after ischemia, we examined the effects of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the neuronal injury of CA1 region induced by 15 min forebrain ischemia using a four-vessel occlusion model. Adult rats received intracerebroventricular administration of either TEA or 4-AP after ischemia or TEA before ischemia and once each day for 7 days. In the postischemic TEA treated-rats, the neuronal injury in hippocampal CA1 region was signifi-cantly less than that of the controls. In contrast, neither preischemic infusion of TEA nor postischemic treatment of 4-AP had any neuroprotective effects. The present study demonstrates that postischemic application of TEA protects hippo-campal CA1 pyramidal neurons against ischemic insult, suggesting that potassium channels may play important roles in the pathogenesis of CA1 neuronal death after transient forebrain ischemia.

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.

The electrophysiological responses of CA3 pyramidal neurons and dentate granule (DG) cells in rat hippocampus were studied after transient forebrain ischemia using intracellular recording and staining techniques in vivo. Approximately 5 min of ischemic depolarization was induced using 4-vessel occlusion method. The spike threshold and rheobase of CA3 neurons remained unchanged up to 12h following reperfusion. No significant change in spike threshold was observed in DG cells but the rheobase transiently increased 6-9h after ischemia. The input resistance and time constant of CA3 neurons increased 0-3h after ischemia and returned to control ranges at later time periods. The spontaneous firing rate in CA3 neurons transiently decreased shortly following reperfusion, while that of DG cells progressively decreased after ischemia. In CA3 neurons, the amplitude and slope of excitatory postsynaptic potentials (EPSPs) transiently decreased 0-3h after reperfusion, and the stimulus intensity threshold for EPSPs transiently increased at the same time. No significant changes in amplitude and slope of EPSPs were observed in DG cells, but the stimulus intensity threshold for EPSPs slightly increased shortly after reperfusion. The present study demonstrates that the excitability of CA3 pyramidal neurons and DG cells after 5min ischemic depolarization is about the same as control levels, whereas the synaptic transmission to these cells was transiently suppressed after the ischemic insult. These results suggest that synaptic transmission is more sensitive to ischemia than membrane properties, and the depression of synaptic transmission may be a protective mechanism against ischemic insults.