S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Master's Degree_의과학과)
STIM1 and SERCA Regulate Spike Frequency Adaptation and Intrinsic Excitability of Mouse Cerebellar Purkinje Neurons
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- Purkinje neuron; spontaneous firing neuron; intrinsic excitability; STIM1; ER Ca2+ store; SERCA
- 학위논문 (석사)-- 서울대학교 대학원 : 의과대학 의과학과, 2018. 2. 김상정.
- 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.