Afterhyperpolarization Promotes the Firing of Mitral Cells through a Voltage-Dependent Modification of Action Potential Threshold
Afterhyperpolarization Promotes the Firing of Mitral Cells through a Voltage-Dependent Modification of Action Potential Threshold
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DOI：
10.1523/eneuro.0401-21.2021
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发表时间：
2022-03-01
期刊：
影响因子：
3.4
通讯作者：
Kuczewski, Nicola
中科院分区：
文献类型：
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作者：
Fourcaud-Trocme, Nicolas;Zbili, Mickael;Kuczewski, Nicola
在嗅球中，二尖瓣细胞（MCs）表现出一种自发放电，其特征是动作电位（APs）的爆发与沉默期的混合。突发内放电频率和持续时间在MCs之间是不均匀的，并且随着膜去极化而增加。通过对大鼠切片进行膜片钳记录，我们剖析了导致这种爆发活动的内在特性。我们发现AP产生的阈值随着膜电位的前导轨迹而动态变化。事实上，当膜处于超极化状态时，AP阈值变得更负，并且恢复速率与膜复极化速率成反比。这种变化似乎是由电压依赖性Na+通道失活状态的变化产生的。因此，超极化事件（如负膜振荡或抑制性突触输入）有利于AP的起始。在第一次AP之后，随后的快速后超极化（AHP）将阈值带到更负的值，然后促进后续AP的发射。这种现象在爆发的每个AP中重复出现，使得快速AHP成为维持发射的再生机制，具有更大振幅和更快复极化的AHP与更大和更高频率的爆发相关。发现突发终止是由于AHP的慢复极化成分的发展（慢AHP）。总体而言，AHP特征似乎是爆破性质的主要决定因素。
In the olfactory bulb, mitral cells (MCs) display a spontaneous firing that is characterized by bursts of action potentials (APs) intermixed with silent periods. Intraburst firing frequency and duration are heterogeneous among MCs and increase with membrane depolarization. By using patch-clamp recording on rat slices, we dissected out the intrinsic properties responsible for this bursting activity. We showed that the threshold of AP generation dynamically changes as a function of the preceding trajectory of the membrane potential. In fact, the AP threshold became more negative when the membrane was hyperpolarized and had a recovery rate inversely proportional to the membrane repolarization rate. Such variations appeared to be produced by changes in the inactivation state of voltage-dependent Na+ channels. Thus, AP initiation was favored by hyperpolarizing events, such as negative membrane oscillations or inhibitory synaptic input. After the first AP, the following fast afterhyperpolarization (AHP) brought the threshold to more negative values and then promoted the emission of the following AP. This phenomenon was repeated for each AP of the burst making the fast AHP a regenerative mechanism that sustained the firing, AHP with larger amplitudes and faster repolarizations being associated with larger and higher-frequency bursts. Burst termination was found to be because of the development of a slow repolarization component of the AHP (slow AHP). Overall, the AHP characteristics appeared as a major determinant of the bursting properties.