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Ion Channels and Excitable Membranes

開催日 2014/9/11
時間 16:00 - 17:00
会場 Poster / Exhibition(Event Hall B)

The Kv2.1 voltage-gated potassium channel regulates action potentials in cerebellar Purkinje cells

  • P1-006
  • 李 源 / Yuan Li:1 渡辺 祥司 / Shoji Watanabe:1 御園生 裕明 / Hiroaki Misonou:1 廣野 守俊Moritoshi Hirono 
  • 1:同志社大学大学院・脳科学研究科・チャネル病態生理部門 / Laboratory of Ion Channel Pathophysiology, Graduate School of Brain Science, Doshisha University, Kyoto, Japan 

Each type of brain neurons expresses a specific set of voltage-gated potassium (Kv) channels to shape action potentials and to set unique firing properties. Among these channels, the Kv2 delayed rectifier channels, Kv2.1 and Kv2.2, are of particular interest due to their wide-spread expression in the brain, high-threshold activation, slow activation and deactivation kinetics, and the dynamic functional modulation via posttranslational modifications. Despite these unique characteristics, their physiological roles in the regulation of neuronal firing are still largely unknown. However, recent studies in rat cortical and hippocampal pyramidal neurons, and neurons in the medial nucleus of the trapezoid body showed that Kv2 inhibition results in increased inter-spike potentials (ISPs) during a train of action potentials. These studies proposed that Kv2 channels keep ISPs well repolarized and therefore ensure the availability of voltage-gated sodium channels, thereby regulating the spike frequencies.
In this study, we investigate the role of Kv2 channels in cerebellar Purkinje cells (PCs). Because PCs exhibit unique high frequency firing and calcium spikes, we speculated that Kv2 channels might serve different roles in these cells. Interestingly, only Kv2.1, but not Kv2.2, is detectable in the somata and proximal dendrites of PCs evidenced by our immunohistochemical data and in situ data from Allen Brain Atlas. To elucidate the role of Kv2.1 in PCs, we examined the effects of a selective Kv2 blocker, Guangxitoxin-1E, as well as its derivatives on action potentials evoked by square current injections into PCs of mouse cerebellar slices with whole-cell current-clamp recordings. In the preliminary experiments, we found that the blockers of Kv2 channels unexpectedly hyperpolarized ISPs and significantly decreased the firing frequency in PCs. These are very different effects of the blockers from what reported in the other types of neurons. We will show and discuss about our electrophysiological data and propose a novel role of Kv2 channels in regulating the action potential firing in PCs.

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