• Archives of Pharmacal Research
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• v.28 no.4
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• pp.413-420
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• 2005

We previously demonstrated the ability of ginseng saponins (active ingredients of Panax ginseng) to enhance $Ca^{2+}$-activated $Cl^{-}$ current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of $Ca^{2+}$ from $IP_{3}-sensitive$ intracellular stores through the activation of PTX-insensitive $G\alpha_{q/11}$ proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates $IP_{3}$ receptor-mediated $Ca^{2+}$ release in both $Ca^{2+}-dependent$ and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current responses in Xenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement was dose- and time-dependent, with an $IC_{50} of 14.9\pm3.5 {\mu}M$. The inhibitory effect of CaM on saponin's activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be $16.7\pm4.3 h$. Intraoocyte injection of CaM inhibited $Ca^{2+}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement and also attenuated $IP_{3}$-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. $Ca^{2+}$/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced $Ca^{2+}$-activated $Cl^{-}$ current enhancement. These results suggest that CaM regulates ginseng saponin effect on $Ca^{2+}$-activated $Cl^{-}$ current enhancement via $Ca^{2+}$-independent manner.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.15 no.5
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• pp.486-492
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• 2004

In this paper, we newly propose the binary CA-CDMA(constant amplitude CDMA) system using pre-coding method to solve the high PAPR problem caused by multi-user signal transmission in the CDMA system. 4-user CA-CDMA, the basis of proposed binary CA-CDMA system, makes binary output signal for 4 input users. It produces the output of binary(${\pm}$2) amplitude by using a parity signal resulting from the XOR operation of 4 users data. Another sub-channel or more bandwidth is not necessary because it is transmitted together with user data and can be easily recovered in the receiver. The extension of the number of users can be possible by the simple repetition of the basic binary 4-user CA-CDMA. For example, binary 16-user CA-CDMA is made easily by allocating the four 4-user CA-CDMA systems in parallel and leading the four outputs to the fifth 4-user CA-CDMA system as input, because the output signal of each 4-user CA-CDMA is also binary. By the same extension procedure, binary 64 and 256-user CA-CDMA systems can be made with the constant amplitude. As a result, the code rate of this proposed CA-CDMA system is just 1 and binary CA-CDMA does not change the transmission rate with the constant output signal(PAPR = 0 ㏈). Therefore, the power efficiency of the HPA can be maximized without the nonlinear distortion. From the simulation results, it is verified that the conventional CDMA system has multi-level output signal, but the proposed binary CA-CDMA system always produces binary output. And it is also found that the BER of conventional CDMA system is increased by nonlinear HPA, but the BER of proposed binary CA-CDMA system is not changed.

• Exercise Science
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• v.26 no.3
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• pp.229-237
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• 2017

PURPOSE: This study was to investigate the Glycolysis mediated sarcoplasmic reticulum (SR) $Ca^{2+}$ signal regulates mitochondria $Ca^{2+}$ during skeletal muscle contraction by using glycolysis inhibitor. METHODS: To examine the effect of Glycolysis inhibitor on SR and mitochondria $Ca^{2+}$ content, we used skeletal muscle fiber from gastrocnemius muscle. 2-deoxy glucose and 3-bromo pyruvate used as glycolysis inhibitor, it applied to electrically stimulated muscle contraction experiment. Intracellular $Ca^{2+}$ content, SR, mitochondria $Ca^{2+}$ level and mitochondria membrane potential (MMP) was detected by confocal microscope. Mitochondrial energy metabolism related enzyme, citric acid synthase activity also examined for mitochondrial function during the muscle contraction. RESULTS: Treatment of 2-DG and 3BP decreased the muscle contraction induced SR $Ca^{2+}$ increase however the mitochondria $Ca^{2+}$ level was increased by treatment of inhibitors and showed and overloading as compared with the control group. Glycolysis inhibitor and thapsigargin treatment showed a significant decrease in MPP of skeletal muscle cells compared to the control group. CS activity significantly decreased after pretreatment of glycolysis inhibitor during skeletal muscle contraction. These results suggest that regulation of mitochondrial $Ca^{2+}$ levels by glycolysis is an important factor in mitochondrial energy production during skeletal muscle contraction CONCLUSIONS: These results suggest that mitochondria $Ca^{2+}$ level can be regulated by SR $Ca^{2+}$ level and glycolytic regulation of intraocular $Ca^{2+}$ signal play pivotal role in regulation of mitochondria energy metabolism during the muscle contraction.

• Toxicological Research
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• v.16 no.1
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• pp.63-66
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• 2000

The effects of acute ethanol on the high K+ induced $Ca^{2+}}$ signals were examined from primary cultures of cerebellar granule neurons. $Ca^{2+}}$ signals were measured with Calcium Green-1 based microscopic video imaging. Because $Ca^{2+}}$ signal was low in most of granule neurons without stimuli, high KCI was used for depolarization. In most case, acute exposure to ethanol reduced the peak amplitude of the $Ca^{2+}}$ signals, induced by high K+, even though low concentration of ethanol(2~10mM) was used and the effects lasted more than 30min. In was also possible to see differences of ethanol inhibition, i.e. the temporal pattern of $Ca^{2+}}$ signal reductions and the strength of inhibition of $Ca^{2+}}$ signals in cerebellar granule neurons. These results indicate that low concentration of ethanol has diverse actions on the $Ca^{2+}}$ signals in cerebellar granule neurons.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.327-334
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• 2017

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established $Ca^{2+}$ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular $Ca^{2+}$ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular $Ca^{2+}$ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than $10{\mu}m$, induced intracellular $Ca^{2+}$ signaling, which was mediated by extracellular $Ca^{2+}$. The PM10-mediated intracellular $Ca^{2+}$ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

• The Journal of Korean Physical Therapy
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• v.19 no.4
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• pp.1-14
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• 2007

Background: It is generally accepted that skeletal muscle contraction is triggered by nerve impulse and intracellular $Ca^{2+}\;([Ca^{2+}]_i)$ released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR). Specifically, this process, called excitation-contraction (E-C) coupling, takes place at intracellular junctions between the plasma membrane, the transverse (T) tubule L-type $Ca^{2+}$ channel (dihydropyridine-sensitive L-rype $Ca^{2+}$ channel, DHPR, also called tetrads), and the SR $Ca^{2+}$ release channel (ryanodine-sensitive $Ca^{2+}$ release channel, RyR, also called feet) of internal $Ca^{2+}$ stores in skeletal muscle cells. Furthermore, it has been reported that the $Ca^{2+-}$ dependent and -independent contraction determine the expression of skeletal muscle genes, thus providing a mechanism for tightly coupling the extent of muscle contraction to regulation of muscle plasticity-related excitation-transcription (E-T) coupling. Purpose: Expression and activity of plasticity-associated enzymes in gastrocnemius muscle strips have not been well studied, however. Methods: Therefore, in this study the expression and phosphorylation of E-C and E-T coupling-related mediators such as protein kinases, ROS(reactive oxygen species)- and apoptosis-related substances, and others in gastrocnemius muscles from rats was examined. Results: I found that expression and activity of MAPKs (mitogen-activated protein kinases, ERK1/2, p38MAPK, and SAPK/JNK), apoptotic proteins (cleaved caspase-3, cytochrome c, Ref-1, Bad), small GTP-binding proteins (RhoA and Cdc42), actin-binding protein (cofilin), PKC (protein kinase C) and $Ca^{2+}$ channel (transient receptor potential channel 6, TRPC6) was observed in rat gastrocnemius muscle strips. Conclusion: These results suggest that MAPKs, ROS- and apoptosis-related enzymes, cytoskeleton-regulated proteins, and $Ca^{2+}$ channel may in part functionally import in E-C and E-T coupling from rat skeletal muscles.

• Journal of the Korean Institute of Telematics and Electronics S
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• v.34S no.11
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• pp.148-155
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• 1997

Ths signal processing technqiue of FET type electrolyte sensors using the back propagation neural network was studied to reduce the interference effects of the different electrolytes. The FET-type electrolyte sensors, pH-ISFET, K-ISFET, and Ca-ISFET, were prepared to measure the pH, K, and Ca electrolytes. Neural network consisted of three layers was learned with 8 patterns and 9 patterns. The sensor output obtained with arbitrary concentrations was processed by the learned neural network. The errors obtained from calibration curve for pH, K, and Ca were .+-.0.039 pH, .+-.2.508 mmol/l, and .+-.1.807 mmol/l, respectively, without considering the interference effects. The errors of the network output for pH, K, and Ca were reduced to .+-.0.005 pH, .+-.0.436 mmol/l, and .+-.0.381 mmol/l in case of 9 patterns, respectively. the signal processing using the neural network can reduce the errors ofthe electrolyte sensor outputs caused by the interference effect, thereby providing effectiveness in the improvement of the sensor selectivity.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.53-53
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• 2003

Calumenin was previously identified as a high affinity Ca$\^$2+/ binding protein in mouse cardiac sarcoplasmic reticulum (SR). For the present study, a 48 kDa skeletal homologue of calumenin was identified by sucrose-density gradient of rabbit skeletal SR membranes, concanavalin A treatment, 2D-gel electrophoresis, $\^$45/Ca$\^$2+/ overlay, Stains-all staining, and MALDI-TOF analysis. We attempted to clone the skeletal calumenin by RT-PCR based on mouse cardiac and human calumenin sequences. The deduced amino acid sequence (315 residues) of the skeletal calumenin showed high identity to mouse cardiac calumenin (90％). As seen in the cardiac calumenin, the deduced sequence contains a 19 amino acid N-terminal signal sequence and a HDEF C-terminal sequence, a putative retrieval signal to ER. Also, the skeletal calumenin contains one N-glycosylation site, three PKC phosphorylation sites, eight casein kinase 2 phosphorylation sites, and 6 EF-hand domains. GST-calumenin showed a conformational change and increased mobility in the presence of Ca$\^$2+/ in SDS-PAGE. Three calumenin interacting proteins (ryanodine receptor 1, glycogen phosphorylase, and phosphofructo kinase) were identified by pull-down assay with GST-calumenin and solubilized SR. All the interactions were Ca$\^$2+/dependent. The present results suggest that calumenin plays an important role in Ca$\^$2+/ homeostasis of muscle cells.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.24-31
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• 2013

Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular $Ca^{2+}$ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular $Ca^{2+}$ concentration in a dose-related fashion. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and melanin synthesis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular $Ca^{2+}$ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.

• Proceedings of the Ginseng society Conference
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• 2006.05a
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• pp.76-76
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• 2006