Dickson C T, Magistretti J, Shalinsky M H, Fransén E, Hasselmo M E, Alonso A
Department of Neurology and Neurosurgery, Montreal Neurological Institute and McGill University, Montreal, Quebec H3A 2B4, Canada.
J Neurophysiol. 2000 May;83(5):2562-79. doi: 10.1152/jn.2000.83.5.2562.
Various subsets of brain neurons express a hyperpolarization-activated inward current (I(h)) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na(+)-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I(h) because it was resistant to extracellular Ba(2+), sensitive to Cs(+), completely and selectively abolished by ZD7288, and carried by both Na(+) and K(+) ions. I(h) in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba(2+), gradually and completely abolished the subthreshold oscillations, thus directly implicating I(h) in their generation. Using experimentally derived biophysical parameters for I(h) and the low-threshold persistent Na(+) current (I(NaP)) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I(NaP) and I(h) can sustain persistent subthreshold oscillations in SCs. I(NaP) and I(h) operate in a "push-pull" fashion where the delay in the activation/deactivation of I(h) gives rise to the oscillatory process.
脑神经元的各种亚群表达一种超极化激活的内向电流（I(h)），该电流已被证明在单细胞和网络水平上对起搏振荡活动起重要作用。内嗅皮层（EC）II层的星状细胞（SCs）具有一个特征，即这些神经元产生传入海马结构的穿通通路输入的主要成分，它们能够产生持续的、依赖Na(+)的节律性阈下膜电位振荡，这种振荡被认为在实现内嗅 - 海马网络中的θ节律方面起重要作用。SCs还在超极化方向表现出强大的时间依赖性内向整流，这可能有助于这些振荡的产生。我们在体外脑片中对SCs进行全细胞记录，以研究这种内向整流电流的具体生物物理和药理学特性，并阐明其在阈下振荡产生中的潜在作用。在电压钳制条件下，超极化电压阶跃诱发一种缓慢、非失活的内向电流，该电流在去极化时也缓慢失活。这种电流被鉴定为I(h)，因为它对细胞外Ba(2+)有抗性，对Cs(+)敏感，被ZD7288完全且选择性地消除，并且由Na(+)和K(+)离子携带。SCs中的I(h)的激活阈值和反转电位分别约为 -45 mV和 -20 mV。其半激活电压为 -77 mV。重要的是，用ZD7288而非Ba(2+)进行浴灌流，逐渐并完全消除了阈下振荡，从而直接表明I(h)参与了它们的产生。利用实验得出的I(h)和SCs中存在的低阈值持续Na(+)电流（I(NaP)）的生物物理参数，构建了这些神经元的简化模型并模拟了它们的阈下电反应性。这表明I(NaP)和I(h)之间的相互作用可以维持SCs中的持续阈下振荡。I(NaP)和I(h)以“推 - 拉”方式运作，其中I(h)激活/失活的延迟产生了振荡过程。
