Agrawal N, Hamam B N, Magistretti J, Alonso A, Ragsdale D S
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Québec, H3A 2B4, Montreal, Canada.
Neuroscience. 2001;102(1):53-64. doi: 10.1016/s0306-4522(00)00455-3.
Entorhinal cortex layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serves as the main conduit for the flow of information out of the hippocampal formation back to the neocortex and, on the other, it closes a hippocampal-entorhinal loop by projecting upon the superficial cell layers that give rise to the perforant path. Recent in vitro electrophysiological studies have shown that rat entorhinal cortex layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we investigated whether entorhinal cortex layer V cells express a persistent sodium current and sustained sodium channel activity to evaluate the contribution of this activity to the subthreshold behavior of the cells. Sharp-electrode recording in slices demonstrated that layer V cells display tetrodotoxin-sensitive inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regenerative events were also abolished by tetrodotoxin, suggesting that their generation also requires the activation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell voltage-clamp experiments, which revealed that its activation "threshold" was negative by about 10mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel activity, consisting of relatively high-conductance ( approximately 18pS) sustained openings. The presence of a persistent sodium current in entorhinal cortex layer V cells can cause the generation of oscillatory behavior, bursting activity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.
内嗅皮层第V层在颞叶神经回路中占据关键位置，一方面，它是信息从海马结构流出返回新皮层的主要通道，另一方面，它通过投射到产生穿通通路的浅层细胞层形成海马 - 内嗅环路。最近的体外电生理研究表明，大鼠内嗅皮层第V层细胞具有产生阈下振荡以及全或无、低阈值去极化电位的能力。在本研究中，我们通过在大鼠脑片和分离神经元中应用电流钳、电压钳和单通道记录技术，研究内嗅皮层第V层细胞是否表达持续性钠电流和持续性钠通道活性，以评估该活性对细胞阈下行为的贡献。脑片的尖锐电极记录表明，第V层细胞在去极化方向表现出对河豚毒素敏感的内向整流，提示细胞中存在持续性钠电流。河豚毒素也消除了阈下振荡和低阈值再生事件，表明它们的产生也需要激活这种低阈值钠电流。全细胞电压钳实验证实了持续性钠电流的存在，该实验表明其激活“阈值”比瞬态钠电流的“阈值”负约10mV。此外，静态噪声分析和细胞贴附式膜片钳记录表明，全细胞持续性钠电流由持续性钠通道活性介导，该活性由相对高电导（约18pS）的持续开放组成。内嗅皮层第V层细胞中持续性钠电流的存在可导致振荡行为、爆发活动和持续放电的产生；这可能与内嗅皮层参与的记忆编码有关，但在病理情况下，也可能促成癫痫发生和神经退行性变。
