• BMB Reports
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• 제46권6호
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• pp.295-304
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• 2013

Extracellular acidification occurs not only in pathological conditions such as inflammation and brain ischemia, but also in normal physiological conditions such as synaptic transmission. Acid-sensing ion channels (ASICs) can detect a broad range of physiological pH changes during pathological and synaptic cellular activities. ASICs are voltage-independent, proton-gated cation channels widely expressed throughout the central and peripheral nervous system. Activation of ASICs is involved in pain perception, synaptic plasticity, learning and memory, fear, ischemic neuronal injury, seizure termination, neuronal degeneration, and mechanosensation. Therefore, ASICs emerge as potential therapeutic targets for manipulating pain and neurological diseases. The activity of these channels can be regulated by many factors such as lactate, $Zn^{2+}$, and Phe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides by interacting with the channel's large extracellular loop. ASICs are also modulated by G protein-coupled receptors such as CB1 cannabinoid receptors and 5-$HT_2$. This review focuses on the physiological roles of ASICs and the molecular mechanisms by which these channels are regulated.

• BMB Reports
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• 제49권10호
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• pp.542-547
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• 2016

Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. Proton sensing by ASICs has been known to mediate pain, mechanosensation, taste transduction, learning and memory, and fear. In this study, we investigated the differential subcellular localization of ASIC2a and ASIC3 in heterologous expression systems. While ASIC2a targeted the cell surface itself, ASIC3 was mostly accumulated in the ER with partial expression in the plasma membrane. However, when ASIC3 was co-expressed with ASIC2a, its surface expression was markedly increased. By using bimolecular fluorescence complementation (BiFC) assay, we confirmed the heteromeric association between ASIC2a and ASIC3 subunits. In addition, we observed that the ASIC2a-dependent surface trafficking of ASIC3 remarkably enhanced the sustained component of the currents. Our study demonstrates that ASIC2a can increase the membrane conductance sensitivity to protons by facilitating the surface expression of ASIC3 through herteromeric assembly.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.311-323
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• 2023

Ion homeostasis, which is regulated by ion channels, is crucial for intracellular signaling. These channels are involved in diverse signaling pathways, including cell proliferation, migration, and intracellular calcium dynamics. Consequently, ion channel dysfunction can lead to various diseases. In addition, these channels are present in the plasma membrane and intracellular organelles. However, our understanding of the function of intracellular organellar ion channels is limited. Recent advancements in electrophysiological techniques have enabled us to record ion channels within intracellular organelles and thus learn more about their functions. Autophagy is a vital process of intracellular protein degradation that facilitates the breakdown of aged, unnecessary, and harmful proteins into their amino acid residues. Lysosomes, which were previously considered protein-degrading garbage boxes, are now recognized as crucial intracellular sensors that play significant roles in normal signaling and disease pathogenesis. Lysosomes participate in various processes, including digestion, recycling, exocytosis, calcium signaling, nutrient sensing, and wound repair, highlighting the importance of ion channels in these signaling pathways. This review focuses on different lysosomal ion channels, including those associated with diseases, and provides insights into their cellular functions. By summarizing the existing knowledge and literature, this review emphasizes the need for further research in this field. Ultimately, this study aims to provide novel perspectives on the regulation of lysosomal ion channels and the significance of ion-associated signaling in intracellular functions to develop innovative therapeutic targets for rare and lysosomal storage diseases.

• 생명과학회지
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• 제20권4호
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• pp.496-502
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• 2010

산성 식염수 쥐모델은 사람의 섬유근통에 근접한 모델로 제시되고 있다. 포도씨에서 얻은 oligomeric proanthocyanidin complexes (OPC)는 항산화제로 알려져 있다. 저자들은 산성 식염수 모델에서 통증 역치에 대한 OPC의 효과를 연구했다. 좌측 장딴지 근육에 pH 4.0의 산성 식염수 $100\;{\mu}l$를 0일과 5일에 주사했다. 대조군은 pH 7.2의 생리 식염수를 같은 스케줄로 주사했다. 산성 식염수 그룹 10마리를 다시 두 그룹으로 나누어 한 그룹은 멸균 식염수, 다른 한 그룹은 OPC 300 mg/kg를 복강 내 주사했다. 복강 내 주사 한시간 후 다시 통각에 대한 역치를 조사했다. 0일에 비해 7일에서 산성 식염수 모델은 기계적 과통각을 나타냈다(p<0.05). OPC 300 mg/kg를 복강내 주사한 그룹에서 강력한 항통각 효과를 나타냈다(주사측 발바닥, p=0.001; 반대측 발바닥, p=0.002). 면역조직화학 염색상 복강내 식염수를 처치한 대조군에 비해 OPC 처치군에서 대뇌의 M1 및 M2 영역에서 산-감지 이온 통로3의 발현이 감소되었다(p<0.05). 사람의 섬유근통에서 OPC 치료의 효과를 보기 위한 연구가 향후 필요할 것으로 생각된다.