Bowden S E, Fletcher S, Loane D J, Marrion N V
Department of Pharmacology and Medical Research Council Center for Synaptic Plasticity, University of Bristol, Bristol, BS8 1TD, United Kingdom.
J Neurosci. 2001 Oct 15;21(20):RC175. doi: 10.1523/JNEUROSCI.21-20-j0006.2001.
In hippocampal neurons, the firing of a train of action potentials is terminated by generation of the slow afterhyperpolarization (AHP). Recordings from hippocampal slices have shown that the slow AHP likely results from the activation of small-conductance calcium-activated potassium (SK) channels by calcium (Ca(2+)) entry through L-type Ca(2+) channels. However, the relative localization of these two channel subtypes is not known. The cloning and characterization of three subtypes of SK channel has suggested that SK1 may underlie generation of the slow AHP. Using a novel antibody directed against rat SK1 (rSK1), it has been determined that the rSK1 channel is primarily in the soma of hippocampal CA1 neurons. In conjunction with antibodies directed against C (Ca(v)1.2) and D (Ca(v)1.3) class L-type Ca(2+) channel alpha1 subunits, it was observed that rSK1 channels were selectively colocalized with D class L-type channels. This colocalization supports the functional coupling of L-type and SK channels previously observed in cell-attached patches from hippocampal neurons. However, it appears contrary to the slow rise and decay of the slow AHP. Induction of delayed facilitation of L-type Ca(2+) channels in cell-attached patches from hippocampal neurons evoked delayed opening of coupled SK channels. Generation of ensemble currents produced waveforms identical to the ionic current underlying the slow AHP (I(sAHP)). Therefore, these data indicate that the slow AHP is somatic in origin, resulting from delayed facilitation of D class L-type Ca(2+) channels colocalized with rSK1 channels.
在海马神经元中，一串动作电位的发放通过慢后超极化（AHP）的产生而终止。海马切片记录显示，慢AHP可能是由于通过L型钙通道进入的钙（Ca(2+)）激活了小电导钙激活钾（SK）通道所致。然而，这两种通道亚型的相对定位尚不清楚。SK通道三种亚型的克隆和特性研究表明，SK1可能是慢AHP产生的基础。使用一种针对大鼠SK1（rSK1）的新型抗体，已确定rSK1通道主要位于海马CA1神经元的胞体中。结合针对C（Ca(v)1.2）和D（Ca(v)1.3）类L型钙通道α1亚基的抗体，观察到rSK1通道与D类L型通道选择性共定位。这种共定位支持了先前在海马神经元细胞贴附片上观察到的L型和SK通道的功能偶联。然而，这似乎与慢AHP的缓慢上升和衰减相反。在海马神经元细胞贴附片中诱导L型钙通道的延迟易化会引起偶联SK通道的延迟开放。集合电流的产生产生了与慢AHP（I(sAHP)）基础离子电流相同的波形。因此，这些数据表明慢AHP起源于胞体，是由与rSK1通道共定位的D类L型钙通道的延迟易化所致。
