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Unveiling the impact of lysosomal ion channels: balancing ion signaling and disease pathogenesis

  • Yoona Jung;Wonjoon Kim;Na Kyoung Shin;Young Min Bae;Jinhong Wie
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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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.

Identification of phospholipase Cβ downstream effect on transient receptor potential canonical 1/4, transient receptor potential canonical 1/5 channels

  • Ko, Juyeon;Myeong, Jongyun;Kwak, Misun;Jeon, Ju-Hong;So, Insuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.5
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    • pp.357-366
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    • 2019
  • $G{\alpha}_q$-coupled receptor stimulation was implied in the activation process of transient receptor potential canonical (TRPC)1/4 and TRPC1/5 heterotetrameric channels. The inactivation occurs due to phosphatidylinositol 4,5-biphosphate ($PI(4,5)P_2$) depletion. When $PI(4,5)P_2$ depletion was induced by muscarinic stimulation or inositol polyphosphate 5-phosphatase (Inp54p), however, the inactivation by muscarinic stimulation was greater compared to that by Inp54p. The aim of this study was to investigate the complete inactivation mechanism of the heteromeric channels upon $G{\alpha}_q$-phospholipase $C{\beta}$ ($G{\alpha}_q-PLC{\beta}$) activation. We evaluated the activity of heteromeric channels with electrophysiological recording in HEK293 cells expressing TRPC channels. TRPC1/4 and TRPC1/5 heteromers undergo further inhibition in $PLC{\beta}$ activation and calcium/protein kinase C (PKC) signaling. Nevertheless, the key factors differ. For TRPC1/4, the inactivation process was facilitated by $Ca^{2+}$ release from the endoplasmic reticulum, and for TRPC1/5, activation of PKC was concerned mostly. We conclude that the subsequent increase in cytoplasmic $Ca^{2+}$ due to $Ca^{2+}$ release from the endoplasmic reticulum and activation of PKC resulted in a second phase of channel inhibition following $PI(4,5)P_2$ depletion.

Prejunctional Modulation of Non-adrenergic Non-cholinergic Relaxation of the Rabbit Proximal Stomach by Potassium Channels (토끼 위 근위부의 비-아드레날린 비-콜린성 이완반응의 포타슘 체널에 의한 접합전 조절작용)

  • Hong, Eun-Ju;Park, Mi-Sun;Park, Sang-Il;Kim, Myung-Woo;Choi, Su-Kyung;Hong, Sung-Cheul
    • YAKHAK HOEJI
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    • v.41 no.4
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    • pp.399-406
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    • 1997
  • The effects of different $K^+$ channel blockers were investigated on the non-adrenergic non-cholinergic (NANC) relaxations in the circular muscle of the rabbit proximal stomach. Non-selective blockers of $K^+$ channels, 4-aminopyridine (4-AP, 3~30${\mu}M$) and tetraethylammonium (TEA, 100~1000${\mu}M$) significantly enhanced the NANC relaxations in a concentration-dependent manner. The enhancement was more prominent for the NANC relaxations induced by the electric field stimulation (EFS) with lower frequencies. Blockers of large conductance $Ca^{2+}$-activated $K^+$ channels, charybdotoxin and iberiotoxin, a blocker of small conduntance $Ca^{2+}$-activated $K^+$ channels, apamin and a blocker of ATP-sensitive $K^+$ channels, glibenclamide had no effect on the NANC relaxations, respectively. Exogeneous administration of nitric oxide (NO, 1~30${\mu}M$) caused concentration-dependent relaxations which showed a similarity to those obtained with EFS. None of the $K^+$ channel blockers had an effect on the concentration-dependent relaxation in response to NO. These results suggest that prejunctional $K^+$ channels regulate the release of NO from the NANC nerve in the rabbit proximal stomach as the inhibition of prejunctional $K^+$ channels increases the NANC relaxation induced by the EFS.

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A burst-error-correcting decoding scheme of multiple trellis-coded $\pi$/4 shift QPSK for mobile communication channels (이동 통신 채널에서 다중 트렐리스 부호화된 $\pi$/4 shift QPSK의 연집 에러 정정 복호 방식)

  • 이정규;송왕철;홍대식;강창언
    • Journal of the Korean Institute of Telematics and Electronics A
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    • v.32A no.4
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    • pp.24-31
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    • 1995
  • In this paper, the dual-mode burst-error-correcting decoding algorithm is adapted to the multiple trellis-coded .pi./4 shift QPSK in order to achieve the improvement of bit error rate (BER) performance over fading channels. The dual-mode adaptive decoder which combines maximum likelihood decoding with a burst detection scheme usually operates as a Viterbi decoder and switches to time diversity error recovery whenever an uncorrectable error pattern is identified. Rayleigh fading channels and Rician fading channels having the Rician parameter K=5dB are used in computer simulation, and the simulation results are compared with those of interleaving techniques. It is shown that under the constraint of the fixed overall memory quantity, the dual-mode adaptive decoding scheme gains an advantage in the BER performance with respect to interleaving strategies.

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DYNAMIC CHARACTERISTICS OF GAIN-CLAMPED L-BAND EDFA WITH BI-DIRECTIONAL PUMPS (양방향 고정이득 L-BAND EDFA의 응답 특성)

  • IkSangKim
    • Journal of the Korean Geophysical Society
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    • v.4 no.4
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    • pp.297-311
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    • 2001
  • The gain-clamped EDFA has been developed to eliminate the output power change of WDM surving channels to occur with added or dropped channels, which degrades the performance of WDM optical network. It maintains the constant gain of surviving channels when WDM channels are added or dropped in a network amplifying node. In this paper, the bi-directionally pumped gain-clamped EDFA is implemented to compensate the change of the input power by a lasing. The results show that the lasing of a short wavelength and backward propagation is the optimal condition to minimize the transient response of surviving channels in terms of the overshoot and gain saturation due to the inhomogeneous broadening effect.

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Characterization of Voltage-Sensitive Calcium Channels and Insulin Secretion and the effect of 4,4'-Dichlorobiphenyl in RINm5f cells

  • Lee, Ihn-Soon;Hur, Eun-Mi;Sungkwon Chung;Kim, Kyong-Tai
    • Proceedings of the Korean Biophysical Society Conference
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    • 2001.06a
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    • pp.47-47
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    • 2001
  • Opening of $Ca^{2+}$ -channels represents the final common pathway for insulin secretion in pancreatic beta-cells and related cell lines. We investigated voltage-sensitive calcium channels (VSCCs) and insulin secretion in RINm5F, an insulinoma cell line derived from rat pancreatic beta-cells. Several types of VSCCs were identified in RINm5f cells: dihydropyridine-sensitive L-type, $\omega$-conotoxin GVIA-sensitive N-type, $\omega$-agatoxin IVA-sensitive P-type channels, and $\omega$-conotoxin MVIIC sensitive Q-type channels.(omitted)

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Analysis of Influential Factors between Communication Effectiveness and Satisfaction in Internal Communication Channels in Enterprises (기업 내 온라인 커뮤니케이션 채널의 만족도가 커뮤니케이션 효과에 미치는 영향 요인 분석)

  • Ham, Soo Yeon;Kim, Jong Woo
    • Journal of Information Technology Services
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    • v.17 no.4
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    • pp.1-19
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    • 2018
  • Effective internal communication is known to have a positive impact on business performance, but there is a lack of research on the effects of online channels for workplace communication. This study using regression analysis examines how task-technology fit, information richness, self-efficacy, perceived ease of use, and perceived usefulness related to online communication channels affect not only the satisfaction with the tools but also the effectiveness of them. Additionally, we verify how the organizational culture of online and offline communication shows the control effect. As a result, all five variables were positively correlated with internal communication channels satisfaction, and we found that the organizational culture of online and offline communication controls the relationship between online communication channels satisfaction and effectiveness.

Increased Activity of Large Conductance $Ca^{2+}-Activated$ $K^+$ Channels in Negatively-Charged Lipid Membranes

  • Park, Jin-Bong;Ryu, Pan-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.4
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    • pp.529-539
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    • 1998
  • The effects of membrane surface charge originated from lipid head groups on ion channels were tested by analyzing the activity of single large conductance $Ca^{2+}-activated\;K^+$ (maxi K) channel from rat skeletal muscle. The conductances and open-state probability ($P_o$) of single maxi K channels were compared in three types of planar lipid bilayers formed from a neutral phosphatidylethanolamine (PE) or two negatively-charged phospholipids, phosphatidylserine (PS) and phosphatidylinositol (PI). Under symmetrical KCl concentrations $(3{\sim}1,000\;mM)$, single channel conductances of maxi K channels in charged membranes were $1.1{\sim}1.7$ times larger than those in PE membranes, and the differences were more pronounced at the lower ionic strength. The average slope conductances at 100 mM KCl were $251{\pm}9.9$, $360{\pm}8.7$ and $356{\pm}12.4$ $(mean{\pm}SEM)$ pS in PE, PS and PI membranes respectively. The potentials at which $P_o$ was 1/2, appeared to have shifted left by 40 mV along voltage axis in the membranes formed with PS or PI. Such shift was consistently seen at pCa 5, 4.5, 4 and 3.5. Estimation of the effect of surface charge from these data indicated that maxi K channels sensed the surface potentials at a distance of $8{\sim}9\;{\AA}$ from the membrane surface. In addition, similar insulation distance ($7{\sim}9\;{\AA}$) of channel mouth from the bilayer surface charge was predicted by a 3-barrier-2-site model of energy profile for the permeation of $K^+$ ions. In conclusion, despite the differences in structure and fluidity of phospholipids in bilayers, the activities of maxi K channels in two charged membranes composed of PS or PI were strikingly similar and larger than those in bilayers of PE. These results suggest that the enhancement of conductance and $P_o$ of maxi channels is mostly due to negative charges in the phospholipid head groups.

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Presynatic Expression of HCN Channel Subunits in Cerebellar Basket Cells

  • Yi, Jee-Hyun;Park, Kyung-Joon;Kang, Shin-Jung;Shin, Ki-Soon
    • Animal cells and systems
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    • v.11 no.2
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    • pp.199-204
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    • 2007
  • HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, whose gene family consists of four subunits (HCN1-4), mediate depolarizing cation currents and contribute to controlling neuronal excitability. In the present study, immunohistochemical and electrophysiological approaches were used to elucidate the role of HCN channels in the cerebellum. Immunohistochemical labeling for HCN1 and HCN2 channels revealed localized expression of both channels at pinceau, the specialized structure of presynaptic axon terminals of basket cells. To determine the functional role of the presynaptic HCN channels, spontaneous inhibitory postsynaptic currents (IPSCs) were recorded from Purkinje cells, the main synaptic targets of basket cells in the cerebellum. While activation of HCN channels by 8-bromo-cAMP increased amplitude of spontaneous IPSCs, blockade of the activated HCN channels by subsequent ZD7288 application reduced the amplitude of spontaneous IPSCs to the level far below the control. Our results imply that modulation of HCN1 and HCN2 channels in presynaptic terminals of basket cells regulates neurotransmitter release, thereby controlling the excitability of Purkinje cells.

Strategic Analysis of the Multilateral Bargaining for the Distribution Channels with Different Transaction Costs (거래비용이 상이한 복수의 유통채널에 대한 다자간 협상전략에 관한 연구)

  • Cho, Hyung-Rae;Rhee, Minho
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.38 no.4
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    • pp.80-87
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    • 2015
  • The proliferation of the Internet and communication technologies and applications, besides the conventional retailers, has led to a new form of distribution channel, namely home sopping through the telephone, TV, catalog or the Internet. The conventional and new distribution channels have different transaction costs perceived by the consumers in the following perspectives: the accessibility to the product information, the traffic cost and the opportunity cost for the time to visit the store, the possibility of 'touch and feel' to test the quality of the product, the delivery time and the concern for the security for the personal information. Difference in the transaction costs between the distribution channels results in the different selling prices even for the same product. Moreover, distribution channels with different selling prices necessarily result in different business surpluses. In this paper, we study the multilateral bargaining strategy of a manufacturer who sells a product through multiple distribution channels with different transaction costs. We first derive the Nash equilibrium solutions for both simultaneous and sequential bargaining games. The numerical analyses for the Nash equilibrium solutions show that the optimal bargaining strategy of the manufacturer heavily depends not only on the degree of competition between the distribution channels but on the difference of the business surpluses of the distribution channels. First, it is shown that there can be four types of locally optimal bargaining strategies if we assume the market powers of the manufacturer over the distribution channels can be different. It is also shown that, among the four local optimal bargaining strategies, simultaneous bargaining with the distribution channels is the most preferred bargaining strategy for the manufacturer.