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STIM1 and SERCA Regulate Spike Frequency Adaptation and Intrinsic Excitability of Mouse Cerebellar Purkinje Neurons

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Authors

정다윤

Advisor
김상정
Major
의과대학 의과학과
Issue Date
2018-02
Publisher
서울대학교 대학원
Keywords
Purkinje neuronspontaneous firing neuronintrinsic excitabilitySTIM1ER Ca2+ storeSERCA
Description
학위논문 (석사)-- 서울대학교 대학원 : 의과대학 의과학과, 2018. 2. 김상정.
Abstract
Proper regulation of cytosolic calcium is important for various neuronal functions. Endoplasmic reticulum (ER) is the main internal calcium store where cytosolic calcium comes in and out appropriately depending on the situations. Recent studies have discovered that stromal interaction molecule 1 (STIM1), which regulates ER store calcium, is widely expressed in the brain, especially in the cerebellar Purkinje neurons. Previous study showed that STIM1 mediates mGluR1-dependent slow current in Purkinje neurons. However, this experiment could not suggest any convincing role of STIM1 in spontaneously firing neurons. Here, by using Purkinje neuron-specific STIM1 knock out mice (STIM1PKO), I investigated the functional role of STIM1 in Purkinje neuron. It was found that the loss of STIM1 resulted in reduced intrinsic excitability with increased spike frequency adaptation (SFA), which was attributed to altered Ca2+-dependent K+ (Kca) current. Furthermore, blocking Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) altered intrinsic properties of STIM1WT to the same level of STIM1PKO while STIM1PKO was unaffected. These findings suggest that STIM1 plays an important role in regulating proper neuronal firing of Purkinje neuron by handling cytosol calcium with SERCA.
Language
English
URI
https://hdl.handle.net/10371/142302
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