• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.215-219
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• 2007

Small and large conductance $Ca^{2+}$-activated $K^+(SK_{Ca}\;and\;BK_{Ca})$ channels are implicated in the modulation of neuronal excitability. We investigated how changes in peripheral $K_{Ca}$ channel activity affect mechanical sensitivity as well as the afferent fiber type responsible for $K_{Ca}$ channel-induced mechanical sensitivity. Blockade of $SK_{Ca}$ and $BK_{Ca}$ channels induced a sustained decrease of mechanical threshold which was significantly attenuated by topical application of capsaicin onto afferent fiber and intraplantar injection of 1-ethyl-2-benzimidazolinone. NS1619 selectively attenuated the decrease of mechanical threshold induced by charybdotoxin, but not by apamin. Spontaneous flinching and paw thickness were not significantly different after $K_{Ca}$ channel blockade. These results suggest that mechanical sensitivity can be modulated by $K_{Ca}$ channels on capsaicin-sensitive afferent fibers.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.611-616
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• 1998

Although the $Ca^{2+}-activated\;K^+\;(I_{K,Ca})$ channel is known to play an important role in the maintenance of resting membrane potential, the regulation of the channel in physiological condition is not completely understood in vascular myocytes. In this study, we investigated the role of cytoplasmic $Mg^{2+}$ on the regulation of $I_{K,Ca}$ channel in pulmonary arterial myocytes of the rabbit using the inside-out patch clamp technique. $Mg^{2+}$ increased open probability (Po), but decreased the magnitude of single channel current. $Mg^{2+}-induced$ block of unitary current showed strong voltage dependence but increase of Po by $Mg^{2+}$ was not dependent on the membrane potential. The apparent effect of $Mg^{2+}$ might, thus, depend on the proportion between opposite effects on the Po and on the conductance of $I_{K,Ca}$ channel. In low concentration of cytoplasmic $Ca^{2+},\;Mg^{2+}$ increased $I_{K,Ca}$ by mainly enhancement of Po. However, at very high concentration of cytoplasmic $Ca^{2+},$ such as pCa 5.5, $Mg^{2+}$ decreased $I_{K,Ca}$ through the inhibition of unitary current. Moreover, $Mg^{2+}$ could activate the channel even in the absence of $Ca^{2+}.\;Mg^{2+}$ might, therefore, partly contribute to the opening of $I_{K,Ca}$ channel in resting membrane potential. This phenomenon might explain why $I_{K,Ca}$ contributes to the resting membrane potential where membrane potential and concentration of free $Ca^{2+}$ are very low.

• BMB Reports
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• v.44 no.10
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• pp.635-646
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• 2011

Due to its high external and low internal concentration the $Ca^{2+}$ ion is used ubiquitously as an intracellular signaling molecule, and a great many $Ca^{2+}$-sensing proteins have evolved to receive and propagate $Ca^{2+}$ signals. Among them are ion channel proteins, whose $Ca^{2+}$ sensitivity allows internal $Ca^{2+}$ to influence the electrical activity of cell membranes and to feedback-inhibit further $Ca^{2+}$ entry into the cytoplasm. In this review I will describe what is understood about the $Ca^{2+}$ sensing mechanisms of the three best studied classes of $Ca^{2+}$-sensitive ion channels: Large-conductance $Ca^{2+}$-activated $K^+$ channels, small-conductance $Ca^{2+}$-activated $K^+$ channels, and voltage-gated $Ca^{2+}$ channels. Great strides in mechanistic understanding have be made for each of these channel types in just the past few years.

• Clinical and Experimental Reproductive Medicine
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• v.28 no.1
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• pp.13-24
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• 2001

Objective: In muscle and neuronal cells, calcium channels have been classified by electrophysiological and pharmacological properties into (1) voltage-dependent $Ca^{2+}$-channel (1) P/Q-type $Ca^{2+}$-channel (2) N-type $Ca^{2+}$-channel (3) L-type $Ca^{2+}$-channel (4) T-type $Ca^{2+}$-channel (5) R-type $Ca^{2+}$-channel. The present study was done in order to investigate whether there is any difference in $Ca^{2+}$-channel distribution between activated and normally fertilized embryos. Methods: The immunocytochemical method was used to identify the existence of voltage-dependent $Ca^{2+}$-channels in parthenogenetically activated 2-cell embryos by ethanol and $SrCl_2$ treatment. These 2-cell embryos were obtained by exposure to 6% ethanol for 6 min and to 10 mM $SrCl_2$ for 2h. Results: P/Q-type $Ca^{2+}$-channels and L-type $Ca^{2+}$-channels have been identified. Whereas, three type of $Ca^{2+}$-channel P/Q-type, N-type, L-type have been identified in 2-cell embryos fertilized in vivo. Conclusion: Activation by ethanol was faster than those by $SrCl_2$. However, there was difference in DAB staining of the embryos between ethanol and $SrCl_2$ treatment (87.7% and 54.1 %). Intensity of staining was also different between ethanol- and $SrCl_2$-treated group. However, it has not been known why there was some difference in DAB staining and staining intensity in the present study.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.131-135
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• 2005

Potassium channels in human skin fibroblast have been studied as a possible site of Alzheimer disease pathogenesis. Fibroblasts in Alzheimer disease show alterations in signal transduction pathway such as changes in $Ca^{2+}$ homeostasis and/or $Ca^{2+}-activated$ kinases, phosphatidylinositol cascade, protein kinase C activity, cAMP levels and absence of specific $K^+$ channel. However, little is known so far about electrophysiological and pharmacological characteristics of large-conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) channel in human fibroblast (CRL-1474). In the present study, we found Iberiotoxin- and TEA-sensitive outward rectifying oscillatory current with whole-cell recordings. Single channel analysis showed large conductance $K^{+}$ channels (106 pS of chord conductance at +40 mV in physiological $K^+$ gradient). The 106 pS channels were activated by membrane potential and $[Ca^{2+}]_i$, consistent with the known properties of $BK_{Ca}$ channels. $BK_{Ca}$ channels in CRL-1474 were positively regulated by adenylate cyclase activator ($10{\mu}M$ forskolin), 8-Br-cyclic AMP ($300{\mu}M$) or 8-Br-cyclic GMP ($300{\mu}M$). These results suggest that human skin fibroblasts (CR-1474) have typical $BK_{Ca}$ channel and this channel could be modulated by c-AMP and c-GMP. The electrophysiological characteristics of fibroblasts might be used as the diagnostic clues for Alzheimer disease.

• The Korean Journal of Physiology
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• v.27 no.1
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• pp.107-114
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• 1993

Most of voltage operated $Ca^{2+}$ channels can be divided into three types (T-, N-, and L-type), according to the electrical and pharmacological properties. Their distribution is closely related to cell specific functions. Properties of the voltage activated $Ca^{2+}$ current in mouse eggs were examined to classify channel types and to deduce the function by using whole cell voltage clamp technique. $Ca^{2+}$ currents appeared below -40 mV and reached a maximum at -15 mV (half maximum was -31 mV), then decayed rapidly (inactivation time constant ${\tau}=28.2{\pm}9.59$ ms at -10 mV within 50 ms after the onset of step depolarization. Activation and inactivation of the $Ca^{2+}$ channel was steeply dependent on voltage, in a relatively low range of $-70\;mV{\sim}-10 mV,$ half maximum of activation was -31 mV and that of inactivation was -39 mV, respectively. This current was not decreased significantly by nifedipine, a specific dihydropyridine $Ca^{2+}$ channel blocker in the range of $1\;{\mu}M\;to\;100{\mu}M.$ The inhibitory effect of $Ni^{2+}\;on\;Ca^{2+}$ current was greater than that of $Cd^{2+}.$ The conductance of $Ba^{2+}$ through the channel was equal to or lower than that of $Ca^{2+}$ These results implied that $Ca^{2+}$ current activated at a lower voltage in the mouse egg is carried via a $Ca^{2+}$ channel with similar properties that of the T-type channel.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.549-553
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• 1998

Using the planar lipid bilayer method, we investigated the effect of d-tubocurarine (dTC) on the extracellular side of large-conductance $Ca^{2+}-activated\;K^+$ channel from rat brain. When the initial open probability (Po) of the channel was relatively high, dTC decreased channel activity in a concentration dependent manner. In contrast, when the initial Po was lower, sub-micro molar dTC increased channel activity by destabilizing the closed states of the channel. Further addition of dTC up to micro molar range decreased channel activity. This dual effect of dTC implicates that there exist at least two different binding sites for dTC.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.151-157
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• 1994

Intracellular free $Ca^{2+}$ contributes to regulation of various events occurring in vascular smooth muscle cells. One of these events is modulating the membrane iou currents. Single smooth muscle cells were isolated from rabbit mesenteric artery. Three kinds of $Ca^{2+}-activated\;current$ were studied with the patch clamp method. $Ca^{2+}-activated\;K^+\;current$ with a large oscillation was recorded in the depolarized potential range. The single channel conductance of this current was about 250 pS. It was abolished by replacing intracellular $K^+\;with\;Cs^+$. A $Ca^{2+}-activated$ nonselective cation current was observed in both the depolarized and hyperpolarized potential ranges. And it was blocked by replacement of extracellular $Na^+$ with N-methylglucamine (NMG) or extracellular application of $Cd^{2+}$. $Ca^{2+}-activated\;Cl^-\;current$ was revealed in the whole voltage range and was blocked by niflumic acid. These results indicate that at least three kinds of $Ca^{2+}-activated$ ionic currents exist in smooth muscle cells from rabbit superior mesenteric artery.

• Bulletin of Food Technology
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• v.18 no.2
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• pp.52-58
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• 2005

최근 20여년 동안 Panax ginseng의 다양한 효과가 연구 되어져 왔다. Panax ginseng의 주요 활성 성분인 ginsenosides는 오직 인삼에서만 발견되어지는 saponin이다. 최근 들어 신경, 非신경 또는 복합적으로 분포된 세포에서 ginsenoside가 $Ca^2+$, $K^+$,$Na^+$,$Cl^-$ channel이나 ligand gated ionchannel (5-HT3, nicotinic acetylcholine, NMDA receptor)과 같은 다양한 ion channel을 조절하는증거들이 발표되고 있다. Ginsenoside는 voltage-dependent $Ca^2+$, $K^+$,$Na^+$ channel의 활성을 억제하는 반면 $Ca^2+$-activated $Cl^-$ channel이나 $Ca^2+$-activated $K^+$ channel의 활성은 증가 시키는 것으로 나타났다. 또한 흥분성 ligand-gated ion channel인 $5-HT_3$, nicotinic acetylcholine, NMDA receptor의 활성은 억제한다. 본 총설에서는 현재까지 알려진 ion channel 활성에 대한 ginsenoside의 조절작용과 이것으로 인해 어떻게 생물학적 효능과 연결이 되어있는지에 대하여 이야기하고자 한다.