Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons
Calcium-activated potassium channels are selectively coupled to P/Q-type calcium channels in cerebellar Purkinje neurons
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DOI：
10.1523/jneurosci.2915-04.2004
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发表时间：
2004-10-06
影响因子：
5.3
通讯作者：
Khodakhah, K
中科院分区：
文献类型：
--
作者：
Womack, MD;Chevez, C;Khodakhah, K
小脑浦肯野神经元在没有突触传递的情况下自发放电。P/ q型电压门控钙通道和钙活化钾通道是正常自发活动所必需的。阻断P/ q型钙通道自相矛盾地模拟了阻断钙活化钾通道的效果。因此，P/ q型钙通道的一个重要功能是为激活钙活化钾通道提供钙。浦肯野神经元表达几种电压门控钙通道，P/Q型和t型通道对动作电位后总钙输入的贡献相当。在这里，我们证明了钙激活的钾通道只被钙通过P/Q型电压门控钙通道进入激活。即使通过电压门控通道的钙通量通过增加细胞外钙浓度而增加，这种选择性耦合仍然保持。P/Q电流密度的小幅下降可能通过减少钙活化钾通道的募集来改变浦肯野神经元的自发活动。在人类和小鼠动物模型中，降低浦肯野神经元P/Q电流密度的突变也会引起小脑性共济失调。浦肯野神经元自发活动的改变可能是引起这些受试者共济失调的重要因素。
Cerebellar Purkinje neurons fire spontaneously in the absence of synaptic transmission. P/Q-type voltage-gated calcium channels and calcium-activated potassium channels are required for normal spontaneous activity. Blocking P/Q-type calcium channels paradoxically mimics the effects of blocking calcium-activated potassium channels. Thus, an important function of the P/Q-type calcium channels is to provide calcium for activation of calcium-activated potassium channels. Purkinje neurons express several classes of voltage-gated calcium channels, and the P/Q- and T-type channels make comparable contributions to total calcium entry after an action potential. Here we demonstrate that calcium-activated potassium channels are activated exclusively by calcium entering through P/Q- type voltage-gated calcium channels. This selective coupling is maintained even when calcium flux through voltage-gated channels is increased by increasing the extracellular calcium concentration. Small decreases in P/Q current density are likely to alter spontaneous activity of Purkinje neurons via decreased recruitment of calcium-activated potassium channels. In both human and murine animal models, mutations that decrease P/Q current density in Purkinje neurons also cause cerebellar ataxia. Alterations in the spontaneous activity of Purkinje neurons may be an important contributing factor to the ataxia in these subjects.