• Journal of Microbiology and Biotechnology
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• 제21권10호
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• pp.1097-1100
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• 2011

A toxin produced by Pseudomonas tolaasii, tolaasin, causes brown blotch disease in mushrooms. Tolaasin forms pores on the cellular membrane and destroys cell structure. Inhibiting the ability of tolaasin to form ion channels may be an effective method to protect against attack by tolaasin. However, it is first necessary to elucidate the three-dimensional structure of the ion channels formed by tolaasin. In this study, the structure of the tolaasin ion channel was determined in silico based on data obtained from nuclear magnetic resonance experiments.

• Journal of Genetic Medicine
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• 제10권2호
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• pp.81-87
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• 2013

Pseudohypoaldosteronism (PHA), a rare syndrome of systemic or renal mineralocorticoid resistance, is clinically characterized by hyperkalemia, metabolic acidosis, and elevated plasma aldosterone levels with either renal salt wasting or hypertension. PHA is a heterogeneous disorder both clinically and genetically and can be divided into three subgroups; PHA type 1 (PHA1), type 2 (PHA2) and type 3 (PHA3). PHA1 and PHA2 are genetic disorders, and PHA3 is a secondary disease of transient mineralocorticoid resistance mostly associated with urinary tract infections and obstructive uropathies. PHA1 includes two different forms with different severity of the disease and phenotype: a systemic type of disease with autosomal recessive inheritance (caused by mutations of the amiloride-sensitive epithelial sodium channel, ENaC) and a renal form with autosomal dominant inheritance (caused by mutations of the mineralocorticoid receptor, MR). In the kidneys, the distal nephron takes charge of the fine regulation of water absorption and ion handling under the control of aldosterone. Two major intracellular actors necessary for the action of aldosterone are the MR and the ENaC. Impairment of the intracellular aldosterone signal transduction pathway results in resistance to the action of mineralocorticoids, which leads to PHA. Herein, ion handling the distal nephron and the clinico-genetic findings of PHA are reviewed with special emphasis on PHA type 1.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.15-23
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• 2014

Transient receptor potential melastatin 7 (TRPM7) is a member of the melastatin-related subfamily and contains a channel and a kinase domain. TRPM7 is known to be associated with cell proliferation, survival, and development. It is ubiquitously expressed, highly permeable to $Mg^{2+}$ and $Ca^{2+}$, and its channel activity is negatively regulated by free $Mg^{2+}$ and Mg-complexed nucleotides. Recent studies have investigated the relationships between TRPM7 and a number of diseases. TRPM7 regulates cell proliferation in several cancers, and is associated with ischemic cell death and vascular smooth muscle cell (VSMC) function. This review discusses the physiologic and pathophysiologic functions and significance of TRPM7 in several diseases.

• 한국임상수의학회지
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• 제21권2호
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• pp.219-228
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• 2004

심장 전도계에 관련된 심장 질환은 심장 전도계의 원발성 결함이나 형태학적 심장 질환 및 약물 중독 같은 속발성 원인에 의해 발생한다. 특히 선천성 심장 전도 장애의 경우, 이온 채널, 이온 채널에 관련한 세포질성 단백질, gap-junction 단백질, transcription factors (심장 발생에 관련된 유전자들) 및 kinase subunit을 전사하는 유전자의 돌연변이가 원발성 선천성 심장 전도장애의 원인으로 밝혀지고 있다. 사람의 부정맥 발생에 관련된 발병기전에 커다란 진보가 이루어지고 있음에도 불구하고, 개의 경우, 저먼 세퍼드의 급사 증후군 (sudden death syndrome)을 제외한 다른 전도 장애에 대한 연구는 극히 미비한 상태이다. 본 종설에서는 지금까지 밝혀진 심장 부정맥 발생의 분자 유전학적 고찰과 이와 관련된 사람의 유전학적 질환들과 이와 유사한 개의 선천성 심장 전도 장애에 대해 연구 고찰하였다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1998년도 학술발표회
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• pp.34-34
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• 1998

Tolaasin is a channel forming bacterial toxin produced by Pseudomonas tolaasii and causes a brown blotch disease on cultivated oyster mushrooms. When tolaasin molecules form channels in the membranes of mushroom cells, they destroy cellular membrane structure, known as 'colloid osmotic lysis'. In order to understand the molecular mechanisms forming membrane channels by tolaasin molecules, we have investigated the electrophysiological characteristics of tolaasin-induced channels in lipid bilayer.(omitted)

• Journal of Applied Biological Chemistry
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• 제64권4호
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• pp.369-374
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• 2021

느타리버섯의 갈반병은 Pseudomonas tolaasii에 의해 생성된 톨라신 및 이의 유사 펩티드 독소에 의해 발생한다. 톨라신 펩티드들은 세포막에 pore를 형성하고 버섯의 자실체 구조를 파괴한다. 적혈구가 파괴되는 용혈은 톨라신의 세포독성에 의해 일어난다. 톨라신의 용혈활성은 Zn²⁺ 및 Ni²⁺과 같은 금속 이온에 의해 저해된다. 가돌리니움 이온을 첨가하였을 때, 톨라신에 의한 용혈작용에서 1 mM 이하의 농도에서는 용혈작용이 증가하고 그 이상의 농도에서는 저해되는 이중 효과가 나타났다. 가돌리니움 이온에 의한 톨라신 활성저해 기작은 다른 양이온들에 의한 저해기작과 다른 것으로 보인다. 가돌리니움 이온은 음전하를 갖는 막지질들에 결합하여 지질막의 측압을 변화시키는 것으로 보고되어, 톨라신 이온통로의 여닫힘에 직접 작용하기 보다는 막 구조의 단단함을 증가시켜 막에 대한 톨라신 이온통로의 안정성을 감소시키는 것으로 보인다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.277-286
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• 2020

Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin-L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM N-lobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu-593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.463-468
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• 2013

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated $K^+$ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane $A_2$ ($TXA_2$) and hypoxia-activated nonselective cation channel ($I_{NSC}$) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and $TXA_2$-activated $I_{NSC}$ was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased $I_{NSC}$ might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

• The Korean Journal of Physiology and Pharmacology
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• 제23권3호
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• pp.219-227
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• 2019

Polycystic kidney disease 2-like-1 (PKD2L1), polycystin-L or transient receptor potential polycystin 3 (TRPP3) is a TRP superfamily member. It is a calcium-permeable non-selective cation channel that regulates intracellular calcium concentration and thereby calcium signaling. Although the calmodulin (CaM) inhibitor, calmidazolium, is an activator of the PKD2L1 channel, the activating mechanism remains unclear. The purpose of this study is to clarify whether CaM takes part in the regulation of the PKD2L1 channel, and if so, how. With patch clamp techniques, we observed the current amplitudes of PKD2L1 significantly reduced when co-expressed with CaM and $CaM{\triangle}N$. This result suggests that the N-lobe of CaM carries a more crucial role in regulating PKD2L1 and guides us into our next question on the different functions of two lobes of CaM. We also identified the predicted CaM binding site, and generated deletion and truncation mutants. The mutants showed significant reduction in currents losing PKD2L1 current-voltage curve, suggesting that the C-terminal region from 590 to 600 is crucial for maintaining the functionality of the PKD2L1 channel. With PKD2L1608Stop mutant showing increased current amplitudes, we further examined the functional importance of EF-hand domain. Along with co-expression of CaM, ${\triangle}EF$-hand mutant also showed significant changes in current amplitudes and potentiation time. Our findings suggest that there is a constitutive inhibition of EF-hand and binding of CaM C-lobe on the channel in low calcium concentration. At higher calcium concentration, calcium ions occupy the N-lobe as well as the EF-hand domain, allowing the two to compete to bind to the channel.