Bal T, McCormick D A
Institut Alfred Fessard, Centre National de la Recherche Scientifique, Gif sur Yvette, France.
J Neurophysiol. 1997 Jun;77(6):3145-56. doi: 10.1152/jn.1997.77.6.3145.
The participation of a hyperpolarization-activated cationic current in the generation of oscillations in single inferior olive neurons and in the generation of ensemble oscillations in the inferior olive nucleus (IO) of the guinea pig and ferret was investigated in slices maintained in vitro. Intracellular recordings in guinea pig or ferret 10 neurons revealed that these cells could generate sustained endogenous oscillations (4-10 Hz) at hyperpolarized membrane potentials (-60 to -67 mV) after the intracellular injection of a brief hyperpolarizing current pulse. These oscillations appeared as the rhythmic generation of a low-threshold Ca2+ spike that typically initiated one or two fast Na+-dependent action potentials. Between low-threshold Ca2+ spikes was an afterhyperpolarization that formed a "pacemaker" potential. Local application of apamin resulted in a large reduction in the amplitude of the afterhyperpolarization, indicating that a Ca2+-activated K+ current makes a strong contribution to its generation. However, even in the presence of apamin, hyperpolarization of IO neurons results in a "depolarizing sag" of the membrane potential that was blocked by local application of Cs+ or partial replacement of extracellular Na+ with choline+ or N-methyl-D-glucamine+, suggesting that I(h) also contributes to the generation of the afterhyperpolarization. Extracellular application of low concentrations of cesium resulted in hyperpolarization of the membrane potential of IO neurons and spontaneous 5- to 6-Hz oscillations in single, as well as networks, of IO neurons. Application of larger concentrations of cesium reduced the frequency of oscillation to 2-3 Hz or blocked the oscillation entirely. On the basis of these results, we propose that I(h) contributes to single and ensemble oscillations in the IO in two ways: 1) I(h) contributes to the determination of the resting membrane potential such that reduction of I(h) results in hyperpolarization of the membrane potential and an increased propensity of oscillation through removal of inactivation of the low-threshold Ca2+ current; and 2) I(h) contributes to the generation of the afterhyperpolarization and the pacemaker potential between low-threshold Ca2+ spikes.
在体外维持的脑片中，研究了超极化激活的阳离子电流在豚鼠和雪貂单个下橄榄核神经元振荡的产生以及下橄榄核（IO）整体振荡的产生中的作用。豚鼠或雪貂IO神经元的细胞内记录显示，在细胞内注入短暂的超极化电流脉冲后，这些细胞能够在超极化膜电位（-60至-67 mV）下产生持续的内源性振荡（4 - 10 Hz）。这些振荡表现为低阈值Ca2+尖峰的节律性产生，通常引发一两个快速的Na+依赖性动作电位。低阈值Ca2+尖峰之间是一个超极化后电位，形成了一个“起搏器”电位。局部应用阿帕明导致超极化后电位的幅度大幅降低，表明Ca2+激活的K+电流对其产生有很大贡献。然而，即使在存在阿帕明的情况下，IO神经元的超极化也会导致膜电位的“去极化下垂”，这被局部应用Cs+或用胆碱+或N - 甲基 - D - 葡糖胺+部分替代细胞外Na+所阻断，表明I(h)也有助于超极化后电位的产生。细胞外应用低浓度的铯导致IO神经元的膜电位超极化，并在单个以及IO神经元网络中引发5至6 Hz的自发振荡。应用更高浓度的铯会将振荡频率降低到2至3 Hz或完全阻断振荡。基于这些结果，我们提出I(h)以两种方式对IO中的单个和整体振荡做出贡献：1）I(h)有助于静息膜电位的确定，使得I(h)的降低导致膜电位超极化，并通过消除低阈值Ca2+电流的失活而增加振荡倾向；2）I(h)有助于超极化后电位以及低阈值Ca2+尖峰之间的起搏器电位的产生。
