• Molecules and Cells
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• 제25권2호
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• pp.242-246
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• 2008

To assess the role of $\alpha_{1G}$ T-type $Ca^{2+}$ channels in neuropathic pain after L5 spinal nerve ligation, we examined behavioral pain susceptibility in mice lacking $Ca_{V}3.1$ (${\alpha}_{1G}{^{-/-}}$), the gene encoding the pore-forming units of these channels. Reduced spontaneous pain responses and an increased threshold for paw withdrawal in response to mechanical stimulation were observed in these mice. The ${{\alpha}_{1G}}^{-/-}$ mice also showed attenuated thermal hyperalgesia in response to both low-(IR30) and high-intensity (IR60) infrared stimulation. Our results reveal the importance of ${\alpha}_{1G}$ T-type $Ca^{2+}$ channels in the development of neuropathic pain, and suggest that selective modulation of ${\alpha}_{1G}$ subtype channels may provide a novel approach to the treatment of allodynia and hyperalgesia.

• 한국의학물리학회지:의학물리
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• 제12권1호
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• pp.59-70
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• 2001

부신수질 크로마핀세포는 아세틸콜린에 반응하여 카테콜아민을 분비한다. 카테콜아민이 분비되기 위하여는 세포외 칼슘이 절대적으로 필요한데 이는 막전압 의존성 칼슘통로를 통하여 칼슘이 세포 속으로 유입되어야 분비기전이 시작됨을 시사한다. 부신수질 크로마핀 세포를 단일세포로 분리한 후 패치클람프 테크닉을 적용하여 여러 종류의 칼슘통로가 존재한다는 것이 알려져 있으나 아직 종이 달라짐에 따라 다른 칼슘통로가 존재하는 지 여부가 확실하지 않다. 그러므로 본 연구에서는 흰쥐 부신수질 크로마핀 세포를 대상으로 하여 단일 세포 패치클람프 테크닉을 적용하여 이 세포에 존재하는 다양한 칼슘통로의 존재를 확인하고자 하였다. L형 칼슘통로 억제제인 nicardipine, N형 칼슘통로 억제제인 $\omega$-CgTx GVIA, P형 칼슘통로 억제제인 $\omega$-AgaTx IVA를 사용하여 L형, N형, P형 칼슘통로가 흰쥐 부신수질 세포에 존재함을 확인하였고 개개의 칼슘통로가 전체 칼슘전류에 기여하는 정도는 L형 >N형> P형이었다.

• The Korean Journal of Physiology and Pharmacology
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• 제10권2호
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• pp.95-99
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• 2006

Employing electrophysiological and cell proliferation assay techniques, we studied the effects of $Ca^{2+}$ -activated $K^+$ channel modulators on the proliferation of human dermal fibroblasts, which is important in wound healing. Macroscopic voltage-dependent outward $K^+$ currents were found at about -40 mV stepped from a holding potential of -70 mV. The amplitude of $K^+$ current was increased by NS1619, a specific large-conductance $Ca^{2+}$-activated $K^+$ (BK) channel activator, but decreased by iberiotoxin (IBTX), a specific BK channel inhibitor. To investigate the presence of an intermediate-conductance $Ca^{2+}$-activated $K^+$ (IK) channels, we pretreated the fibroblasts with low dose of TEA to block BK currents, and added 1-EBIO (an IK activator). 1-EBIO recovered the currents inhibited by TEA. When various $Ca^{2+}$-activated $K^+$ channel modulators were added into culture media for 1∼3 days, NS1619 or 1-EBIO inhibited the cell proliferation. On the other hand, IBTX, clotrimazole or apamin, a small conductance $Ca^{2+}$-activated $K^+$ channel (SK) inhibitor, increased it. These results suggest that BK, IK, and SK channels might be involved in the proliferation of human dermal fibroblasts, which is inversely related to the channel activation.

• Journal of Communications and Networks
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• 제11권2호
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• pp.175-186
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• 2009

A new medium access control (MAC) scheme embedding physical channels into multiband carrier sense multiple access/collision avoidance (CSMA/CA) networks is proposed to provide strict quality of service (QoS) guarantee to high priority users. In the proposed scheme, two priority classes of users, primary and secondary users, are supported. For primary users physical channels are provided to ensure strict QoS, whereas secondary users are provided with best-effort service using CSMA/CA modified for multiband operation. The performance of the proposed MAC scheme is investigated using a new multiband CSMA/CA Markov chain model capturing the primary user activity and the operation of secondary users in multiple bands. The throughput of secondary users is obtained as a function of the primary user activity and other CSMA/CA parameters. It is shown that the new MAC scheme yields larger throughput than the conventional single-band CSMA/CA when both schemes use the same bandwidth.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.182-189
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• 1998

Administration of ginsenosides, a mixture of saponin extracted from Panax ginseng, decreased blood pressure in rat. Previous studies have shown that ginsenosides caused endothelium-dependent relaxation, which was associated with the formation of cyclic GMP, suggested that ginsenosides caused release of nitric oxide (NO) from the vascular endothelium. The aim of the present study was to characterize the endothelium-independent relaxation to ginsenosides in the isolated rat aorta. Ginsenosides caused a concentration-dependent relaxation of rat aortic rings without endothelium constricted with 25 mM KCI but affected only minimally those constricted with 60 mM KCI. Ginsenoside Rg3 (Rg3) was a more potent vasorelaxing agonist than total ginsenoside mixture and also the ginsenoside PPT and PPD groups. Relaxation to ginsenosides were markedly reduced by TEA, but not by glibenclamide. Rg3 significantly inhibited Cal'-induced concentration-contraction curves and the "50a2'influx in aortic rings incubated in 25 mM KCI whereas those responses were not affected in 60 mM KCI. Rg3 caused efflux of $"Rb in aortic rings that was inhibited by tetraethy- lammonium (TEA), an inhibitor of Ca"-dependent K'channels, but not by glibenclamide, an inhibitor of AfP-dependent K'channels. These findings indicate that ginsenosides may induce vasorelaxation via activation of Ca2'-dependent K'channels resulting in hyperpolarization of the vas- cular smooth muscle with subsequent inhibition of the opening of voltage-dependent Caf'channels. These effects could contribute to explain the red ginseng-associated vasodilation and the beneficial effect on the cardiovascular system.

• Molecules and Cells
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• 제39권4호
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• pp.322-329
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• 2016

Voltage-gated $Ca^{2+}$ ($Ca_V$) channels are dynamically modulated by Gprotein-coupled receptors (GPCR). The $M_1$ muscarinic receptor stimulation is known to enhance $Ca_V2.3$ channel gating through the activation of protein kinase C (PKC). Here, we found that $M_1$ receptors also inhibit $Ca_V2.3$ currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12-myristate 13-acetate (PMA), a PKC activator, potentiated $Ca_V2.3$ currents by ~two-fold. After the PMA-induced potentiation, stimulation of $M_1$ receptors decreased the $Ca_V2.3$ currents by $52{\pm}8%$. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) is responsible for the muscarinic suppression of $Ca_V2.3$ currents by using two methods: the Danio rerio voltage-sensing phosphatase (Dr-VSP) system and the rapamycin-induced translocatable pseudojanin (PJ) system. First, dephosphorylation of $PI(4,5)P_2$ to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed $Ca_V2.3$ currents, by $53{\pm}3%$. Next, dephosphorylation of both PI(4)P and $PI(4,5)P_2$ to PI by PJ translocation further decreased the current by up to $66{\pm}3%$. The results suggest that $Ca_V2.3$ currents are modulated by the $M_1$ receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane $PI(4,5)P_2$. Our results also suggest that there is rapid turnover between PI(4)P and $PI(4,5)P_2$ in the plasma membrane.

• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.511-519
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• 2001

Nimopidine, one of dihydropyridine derivatives, has been widely used to pharmacologically identify L-type Ca currents. In this study, it was tested if nimodipine is a selective blocker for L-type Ca currents in sensory neurons and heterologous system. In mouse dorsal root ganglion neurons (DRG), low concentrations of nimodipine $(<10\;{\mu}M),$ mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by ${\sim}38%.$ Interestingly, high concentrations of nimodipine $(>10\;{\mu}M)$ further reduced the 'residual' currents in DRG neurons from ${\alpha}_{1E}$ knock-out mice, after blocking L-, N- and P/Q-type Ca currents with $10\;{\mu}M$ nimodipine, $1\;{\mu}M\;{\omega}-conotoxin$ GVIA and 200 nM ${\omega-agatoxin$ IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine $(>10\;{\mu}M)$ also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and ${\alpha}_{1B}\;and\;{\alpha}_{1E}$ subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine $(>10\;{\mu}M)$ is not necessarily selective for L-type Ca currents. While care should be taken in using nimodipine for pharmacologically defining L-type Ca currents from native macroscopic Ca currents, nimodipine $(>10\;{\mu}M)$ could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.188.2-188.2
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• 2003

Large-conductance $Ca^{2+}$ activated potassium channels $(BK_{ca})$ are widely distributed and play key roles in various cell functions. In nerve cells, B $K_{ca}$ channels shorten the duration of action potentials and block $Ca^{2+}$ entry thereby repolarizing excitable cells after excitation. $(BK_{ca})$ channel opening has been postulated to confer neuroprotection during stroke and has attracted attention as a means for therapeutic intervention in asthma, hypertension, convulsion, and traumatic brain injury. (omitted)

• BMB Reports
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• 제48권1호
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• pp.1-5
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• 2015

Transient Receptor Potential, Melastatin-related, member 4 (TRPM4) channels are $Ca^{2+}$-activated $Ca^{2+}$-impermeable cation channels. These channels are expressed in various types of mammalian tissues including the brain and are implicated in many diverse physiological and pathophysiological conditions. In the past several years, the trafficking processes and regulatory mechanism of these channels and their interacting proteins have been uncovered. Here in this minireview, we summarize the current understanding of the trafficking mechanism of TRPM4 channels on the plasma membrane as well as heteromeric complex formation via protein interactions. We also describe physiological implications of protein-TRPM4 interactions and suggest TRPM4 channels as therapeutic targets in many related diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.279-283
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• 2011

Quercetin (3,3',4',5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased $BK_{Ca}$ current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration ($IC_{50}$) of quercetin was $45.5{\pm}7.2{\mu}m$. The quercetin-evoked $BK_{Ca}$ current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific $BK_{Ca}$ blocker and iberiotoxin (IBX; 100 nM) a $BK_{Ca}$-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol ($DiBAC_4$2(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect ($30.3{\pm}13.5%$) which was recovered to $53.3{\pm}10.5%$ and $72.9{\pm}3.7%$ by TEA and IBX, respectively. Taken together our results indicate that activation of $BK_{Ca}$ channels may be considered an important target related to the action of quercetin on human bladder cancer cells.