ROLE OF NA-K PUMP POTASSIUM REGULATION AND IPSPS IN SEIZURES AND SPREADING DEPRESSION IN IMMATURE RABBIT HIPPOCAMPAL SLICES

ROLE OF NA-K PUMP POTASSIUM REGULATION AND IPSPS IN SEIZURES AND SPREADING DEPRESSION IN IMMATURE RABBIT HIPPOCAMPAL SLICES
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DOI:
10.1152/jn.1990.63.2.225
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发表时间:
1990-02-01
影响因子:
2.5
通讯作者:
SCHWARTZKROIN, PA
SCHWARTZKROIN, PA
中科院分区:
医学3区
文献类型:
--
作者:
HAGLUND, MM;SCHWARTZKROIN, PA

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1.使用未成熟(出生后8-12天)的兔海马脑片制备,我们研究了自发性和诱发性扩散性抑制(SD)发作期间发生的区域细胞外钾浓度[(K+)]o的变化。我们在此报告了未成熟海马中CA 1和CA 3细胞群在以下方面的差异:1)静息态[K+]o,2)在类癫痫事件和SD期间[K+]o变化的幅度,以及3)对SD发作的易感性。实验还进行了阐明钠钾泵和突触抑制在控制SD发作,持续时间和恢复中发挥的作用。我们证明了钠钾泵对钾离子调节的重要作用,而抑制性突触后电位(IPSPs)在预防CA 3区SD中的调节作用较小。2.在自发或诱发SD过程中,在未成熟兔海马CA 1和CA 3区同时进行细胞内和细胞外记录,而钾离子敏感微电极(K-ISMs)监测[K+]o的变化。CA 1区的自发SD发作频率高于CA 3,2)钾触发SD的阈值较低,3)SD发作持续时间较长,4)SD后膜电位和[K+]o下冲较小(低于原始静息膜电位和静息[K+]o)。3.在SD发作的CA 1区,当地的[K+]O上升之前或同时作为膜电位去极化。4.在CA 3区,自发性发作样事件组成的强直性细胞去极化与重复活动,随后阵挛性后放电更容易发生比SD发作。在这些发作样发作期间,[K+]o上升超过癫痫发作期间成人CNS组织报告的10至12 mM上限水平。由重复刺激诱发的[K+]o增加在CA 3中以较低水平调节(平均[K+]o升高至11.4 mM),而在CA 1中(平均[K+]o升高至18.3 mM)。5.在CA 3中,10 μ M荷包牡丹碱或3.4 mM青霉素的浴应用没有改变自发发生SD的频率或SD对2 M KCl局部压力喷射的反应阈值。然而,IPSPs的阻断确实导致SD或苔藓纤维刺激引起的类似癫痫发作的阈值降低。6.通过局部压力喷射将哇巴因(10 μ M)单次应用于CA 3,导致用K-ISM测量的局部[K+]o缓慢上升。哇巴因处理还增加了自发性突触后电位活动的频率,降低了CA 3锥体细胞后超极化(AHPs)的幅度和持续时间。(400字处删节)
1. Using the immature (8-12 days postnatal) rabbit hippocampal slice preparation, we investigated regional extracellular potassium concentration [( K+]o) changes that occur during spontaneous and evoked spreading depression (SD) episodes. We report here a difference between the CA1 and CA3 cell populations in the immature hippocampus with regard to 1) resting [K+]o, 2) magnitude of the [K+]o change during seizurelike events and SDs, and 3) susceptibility to SD episodes. Experiments were also performed to elucidate the roles that the Na-K pump and synaptic inhibition play in controlling SD onset, duration, and recovery. We demonstrated a major role for potassium regulation by the Na-K pump and a lesser modulatory role for inhibitory postsynaptic potentials (IPSPs) in preventing SD in the CA3 region. 2. Simultaneous intra- and extracellular recordings were made in the CA1 and CA3 regions of the immature rabbit hippocampus during spontaneous or evoked SD, while potassium ion-sensitive microelectrodes (K-ISMs) monitored changes in [K+]o. The CA1 region had 1) a higher frequency of spontaneous SD episodes than CA3, 2) a lower threshold to potassium-triggered SD, 3) a longer duration SD episode, and 4) smaller post-SD membrane potential and [K+]o undershoots (below the original resting membrane potential and resting [K+]o). 3. During the onset of a SD episode in the CA1 region, the local [K+]o rose either before or at the same time as the membrane potential depolarization. 4. In the CA3 region, spontaneous ictallike events consisting of tonic cell depolarization with repetitive activity followed by clonic afterdischarges were more likely to occur than SD episodes. During these ictallike episodes, [K+]o rose above the 10- to 12-mM ceiling level reported for adult CNS tissue during seizures. Increases in [K+]o evoked by repetitive stimulation were regulated at a lower level in CA3 (average [K+]o rise to 11.4 mM) than in CA1 (average [K+]o rise to 18.3 mM). 5. In CA3, bath application of 10 microM bicuculline or 3.4 mM penicillin did not change the frequency of spontaneously occurring SDs or the SD response threshold to local pressure ejection of 2 M KCl. However, blockade of IPSPs did lead to lower thresholds for SD or seizurelike episodes elicited by stimulation of the mossy fibers. 6. A single application of ouabain (10 microM) to CA3 by local pressure ejection caused a slow rise in local [K+]o measured with K-ISMs. The ouabain treatment also increased the frequency of spontaneous postsynaptic potential activity and decreased the amplitude and duration of CA3 pyramidal cell afterhyperpolarizations (AHPs).(ABSTRACT TRUNCATED AT 400 WORDS)