Albany Medical College, Center for Neuropharmacology and Neuroscience, Albany, New York, USA.
J Neurophysiol. 2011 Mar;105(3):1185-98. doi: 10.1152/jn.00770.2010. Epub 2011 Jan 5.
Previously, we found that rat hippocampal CA3 interneurons become hyperactive with increasing concentrations of extracellular K(+) up to 10 mM. However, it is unclear how this enhanced interneuronal activity affects pyramidal neurons. Here we voltage-clamped rat hippocampal CA3 pyramidal neurons in vitro at 0 mV to isolate γ-aminobutyric acid (GABA)-activated inhibitory post-synaptic currents (IPSCs) and measured these in artificial cerebrospinal fluid (aCSF) and with 10 mM K(+) bath perfusion. In aCSF, small IPSCs were present with amplitudes of 0.053 ± 0.007 nA and a frequency of 0.27 ± 0.14 Hz. With 10 mM K(+) perfusion, IPSCs increased greatly in frequency and amplitude, culminating in surge events with peak amplitudes of 0.56 ± 0.08 nA, that appeared and disappeared cyclically with durations lasting 2.02 ± 0.37 min repeatedly, up to 10 times over a 30-min bath perfusion of elevated K(+). These large IPSCs were GABA(A)-receptor mediated and did not involve significant desensitization of this receptor. Perfusion of a GABA transporter inhibitor (NO-711), glutamate receptor inhibitors CNQX and APV, or a gap junctional blocker (carbenoxolone) prevented the resurgence of large IPSCs. Pressure ejected sucrose resulted in the abolishment of subsequent surges. No elevated K(+)-mediated surges were observed in CA3 interneurons from the stratum oriens layer. In conclusion, these cyclic large IPSC events observable in CA3 pyramidal neurons in 10 mM KCl may be due to transient GABA depletion from continuously active interneuronal afferents.
先前，我们发现，随着细胞外液 K+浓度的增加（高达 10mM），大鼠海马 CA3 中间神经元变得过度活跃。然而，这种增强的中间神经元活性如何影响锥体神经元尚不清楚。在这里，我们在 0mV 下对大鼠海马 CA3 锥体神经元进行电压箝制，以分离γ-氨基丁酸（GABA）激活的抑制性突触后电流（IPSCs），并在人工脑脊液（aCSF）和 10mM K+灌流中测量这些电流。在 aCSF 中，存在幅度为 0.053±0.007nA、频率为 0.27±0.14Hz 的小 IPSCs。用 10mM K+灌流时，IPSCs 的频率和幅度大大增加，最终出现峰值幅度为 0.56±0.08nA 的涌流事件，这些事件以持续 2.02±0.37min 的周期出现和消失，在 30min 的高钾浴灌流中重复多达 10 次。这些大 IPSCs 是 GABA(A)受体介导的，并且这种受体没有明显的脱敏。GABA 转运体抑制剂（NO-711）、谷氨酸受体抑制剂 CNQX 和 APV 或缝隙连接阻滞剂（carbenoxolone）的灌流可防止大 IPSCs 的再次出现。压力喷出蔗糖可导致随后的涌流消失。在来自层状或区层的 CA3 中间神经元中未观察到升高的 K+介导的涌流。总之，在 10mM KCl 中可观察到 CA3 锥体神经元中的这些周期性大 IPSC 事件可能是由于持续活跃的中间神经元传入导致 GABA 短暂耗竭。
