KV10.1 opposes activity-dependent increase in Ca2+ influx into the presynaptic terminal of the parallel fibre-Purkinje cell synapse
KV10.1 opposes activity-dependent increase in Ca2+ influx into the presynaptic terminal of the parallel fibre-Purkinje cell synapse
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DOI：
10.1113/jphysiol.2014.281600
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发表时间：
2015-01-01
影响因子：
5.5
通讯作者：
Pardo, Luis A.
中科院分区：
文献类型：
--
作者：
Mortensen, Lena Suenke;Schmidt, Hartmut;Pardo, Luis A.
电压门控钾通道K(V)10.1 (Eag1)在哺乳动物大脑中广泛表达，但其生理功能尚不清楚。先前的研究揭示了海马体和小脑中的最高表达水平，并表明该通道的突触定位。 K(V)10.1 独特的激活动力学表明其在细胞重复活动中发挥作用。在这里，我们在生化和功能上确认了 K(V)10.1 的突触定位，并且该通道在生理温度下足够快，足以参与动作电位 (AP) 的复极化。我们使用膜片钳和双光子 Ca2+ 成像在 K(V)10.1 缺陷型和野生型小鼠中研究了该通道在小脑生理学中的作用。颗粒细胞体细胞记录的兴奋性和动作电位波形没有变化，而突变体中 Ca2+ 流入轴突的波团在响应三个 AP 刺激后增强，但在单个 AP 刺激后则没有增强。此外，突变体在高放电率下平行纤维浦肯野细胞突触的促进作用表现出频率依赖性的增加。我们建议 K(V)10.1 作为局部 AP 形状的调制器，特别是在其他钾通道遭受累积失活的高频突发放电期间。
The voltage-gated potassium channel K(V)10.1 (Eag1) is widely expressed in the mammalian brain, but its physiological function is not yet understood. Previous studies revealed highest expression levels in hippocampus and cerebellum and suggested a synaptic localization of the channel. The distinct activation kinetics of K(V)10.1 indicate a role during repetitive activity of the cell. Here, we confirm the synaptic localization of K(V)10.1 both biochemically and functionally and that the channel is sufficiently fast at physiological temperature to take part in repolarization of the action potential (AP). We studied the role of the channel in cerebellar physiology using patch clamp and two-photon Ca2+ imaging in K(V)10.1-deficient and wild-type mice. The excitability and action potential waveform recorded at granule cell somata was unchanged, while Ca2+ influx into axonal boutons was enhanced in mutants in response to stimulation with three APs, but not after a single AP. Furthermore, mutants exhibited a frequency-dependent increase in facilitation at the parallel fibre-Purkinje cell synapse at high firing rates. We propose that K(V)10.1 acts as a modulator of local AP shape specifically during high-frequency burst firing when other potassium channels suffer cumulative inactivation.