• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.529-535
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• 1997

The present study was aimed at investigating whether the vascular calcium regulation is altered in hypertension. Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were made in rats, and their thoracic aortae were taken 4 weeks later. The isometric contractile response and calcium uptake of the endothelium-denuded aortic preparations were determined. Caffeine ($0.1{\sim}35\;mmol/L$) induced a greater contraction in 2K1C and DOCA-salt hypertension than in normotensive control. When the vascular calcium store was functionally-depleted by a repeated exposure to caffeine, it took longer to reload the store and to resume the initial contraction force in response to caffeine in both 2K1C and DOCA-salt hypertension. The vascular $^{45}Ca$ uptake following the functional depletion of the cellular store was also greater in both models of hypertension than in control. Ryanodine, calcium channel activator of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced vascular contraction, which was not affected by either 2K1C or DOCA-salt hypertension. Nifedipine, an L-type $Ca^{2+}$ channel blocker, attenuated the restoration of caffeine-induced contraction, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Nifedipine also diminished the vascular $^{45}Ca$ uptake, which was not affected by DOCA-salt hypertension, but was more pronounced in 2K1C hypertension. Ouabain, a $Na^+,\;K^+-ATPase$ inhibitor, increased the caffeine-induced contraction by a similar magnitude in control and 2K1C hypertension, which was, however, markedly attenuated in DOCA-salt hypertension. Ouabain enhanced the vascular $^{45}Ca$ uptake, the degree of which was not affected by 2K1C hypertension, but was markedly attenuated in DOCA-salt hypertension compared with that in control. Cyclopiazonic acid, a selective inhibitor of $Ca^{2+}-ATPase$ of the sarcoplasmic reticulum, attenuated the restoration of caffeine-induced contraction, which was not affected by 2K1C hypertension, but was more marked in DOCA-salt hypertension. These results suggest that the increased vascular calcium storage may be attributed to an enhanced calcium influx in 2K1C hypertension, and to an impaired $Na^+-K^+$ pump activity of the cell membrane and subsequently increased calcium pump activity of the cellular store in DOCA-salt hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.3
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• pp.143-147
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• 2002

Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of $Na^+$ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic $Na^+$ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about $-49.04{\pm}1.69\;mV\;(n=43,\;mean{\pm}SD)$ and lasting $3{\sim}7$ ms. Increase of extracellular $Ca^{2+}$ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A $K^+$ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM $Ca^{2+}$ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external $Ca^{2+},$ even in the presence of 4-AP (2 mM). A $Na^+$ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular $Ca^{2+}$ influx contributes to the generation of ADP in granule cells.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.103-108
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• 2005

To study the direct effect of somatostatin (SS) on calcium channel current ($I_{Ba}$) in guinea-pig gastric myocytes, $I_{Ba}$ was recorded by using whole-cell patch clamp technique in single smooth muscle cells. Nicardipine ($1{\mu}M$), a L-type $Ca^{2+}$ channel blocker, inhibited $I_{Ba}$ by $98{\pm}1.9$% (n=5), however $I_{Ba}$ was decreased in a reversible manner by application of SS. The peak $I_{Ba}$ at 0 mV were decreased to $95{\pm}1.5$, $92{\pm}1.9$, $82{\pm}4.0$, $66{\pm}5.8$, $10{\pm}2.9$% at $10^{-10}$, $10^{-9}$, $10^{-8}$, $10^{-7}$, $10^{-5}$ M of SS, respectively (n=3∼6; $mean{\pm}SEM$). The steady-state activation and inactivation curves of $I_{Ba}$ as a function of membrane potentials were well fitted by a Boltzmann equation. Voltage of half-activation ($V_{0.5}$) was $-12{\pm}0.5$ mV in control and $-11{\pm}1.9$ mV in SS treated groups (respectively, n=5). The same values of half-inactivation were $-35{\pm}1.4$ mV and $-35{\pm}1.9$ mV (respectively, n=5). There was no significant difference in activation and inactivation kinetics of $I_{Ba}$ by SS. Inhibitory effect of SS on $I_{Ba}$ was significantly reduced by either dialysis of intracellular solution with $GDP_{\beta}S$, a non-hydrolysable G protein inhibitor, or pretreatment with pertussis toxin (PTX). SS also decreased contraction of guinea-pig gastric antral smooth muscle. In conclusion, SS decreases voltage-dependent L-type calcium channel current ($VDCC_L$) via PTXsensitive signaling pathways in guinea-pig antral circular myocytes.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.158.2-159
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• 2003

Cadmium is well known as a toxic metal and has insulin mimicking effects in rat adipose tissue. To investigate the effect of CdCl2 on glucose transport and its mechanism, this study was performed in 3T3-L1 adipocytes. 10 and 25mM of CdCl2 exposed to cells for 12 hours increased 2-deoxyglucose uptake to 2.2 and 2.8 fold, respectively. Nifedipine, a calcium channel blocker, inhibited the 2-deoxyglucose uptake stimulated by CdCl2. (omitted)

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2274-2278
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• 2011

Verapamil is a calcium channel blocker and is classified as a class IV anti-arrhythmic agent. It is used in the control of supra ventricular tachyarrhythmias, and in the management of classical and variant angina pectoris. It is also used in the treatment of hypertension and used as an important therapeutic agent for angina pectoris, ischemic heart disease, hypertension and hypertrophic cardiomyopathy. Verapamil commonly co-administered with NSAIDs (non-steroidal anti-inflammatory drugs) i.e. diclofenac sodium, flurbiprofen, Ibuprofen, mefanamic acid and meloxicam. A simple and rapid RP-HPLC method for simultaneous determination and quantification of verapamil and NSAIDs was developed and validated. The mobile phase constituted of acetonitrile: water (55:45) whose pH was adjusted at 2.7 and pumped at a flow rate of 2.0 mL $min^{-1}$ at 230 nm. The proposed method is simple, precise, accurate, low cost and least time consuming for the simultaneous determination of verapamil and NSAIDs which can be effectively applied for the analysis of human serum.

• The Korean Journal of Physiology
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• v.24 no.2
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• pp.353-362
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• 1990

Fluoride (F-), a known stimulator of G-protein, induced strong contraction in rabbit trachealis muscle. $AlCl_3\;(5{\sim}20\;{\mu}M)$, which is required for G-protein stimulation by $F^-$, potentiated the contractile response to $F^-$. $Ca^{2+}-removal$ and verapamil, a calcium channel blocker, inhibited the fluoroaluminate-induced contraction. Fluoroaluminate increased $^{45}Ca$ influx in the absence and presence of verapamil. In heparin-loaded muscle high $K^+-induced$ contraction was not affected, but acetylcholine and fluoroaluminate-induced contractions were inhibited. The fluoroaluminate-induced contraction was partially relaxed by isoproterenol, a stimulator of adenylate cyclase. Pertussis toxin partially inhibited fluoroaluminate-induced contraction and potentiated isoproterenol-induced relaxation in the presence of fluoroaluminate, but had no effect on acetylcholine-induced contraction and the isoproterenol-induced relaxation in the presence of acetylcholine. These results suggest that fluoroaluminate has the ability to stimulate at least two putative G-proteins in rabbit trachealis muscle; One causes $Ca^{2+}$ influx through the potential-operated $Ca^{2+}$ channel and the other induces intracellular $Ca^{2+}$ release by the increase of inositol-1, 4, 5-triphosphate.

• Journal of Plant Biotechnology
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• v.34 no.3
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• pp.213-221
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• 2007

The treatment of radish cotyledons with a nitric oxide (NO)-releasing substance, sodium nitroprusside (SNP) resulted in an increased adventitious root development in a dose-dependent manner. However, this NO-mediated enhancement effect was reversed when either 0.5 mM EGTA (an extracellular $Ca^{2+}$ chelator) or 0.1 mM $LaCl_3$ (a calcium channel blocker) was applied with $50\;{\mu}M$ SNP. Our results also showed that guaiacol peroxidase (GPX) and syringaldazine peroxidase (SPX) activities, which are known to play a key role in rooting, were more largely increased during adventitious root induction in the cotyledons treated with SNP. However, the treatment of cotyledons with SNP plus $LaCl_3$ inhibited the SNP-induced increases in the activities of both GPX and SPX. Trifluoperazine (TFP), an antagonist of calmodulin (a specific calcium-binding protein), also delayed adventitious root formation and significantly reduced the root length and number of the SNP-treated cotyledons as well as the deactivation of GPX and SPX enzymes. In conclusion, our results suggest that calcium is involved in the NO response leading to induction of adventitious root through a regulation of GPX and SPX.

• Journal of Korean Neurosurgical Society
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• v.38 no.5
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• pp.375-379
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• 2005

Objective : Papaverine has been used in treating vasospasm following subarachnoid hemorrhage[SAH]. However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. Methods : The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. Results : Papaverine of $100{\mu}M$ into bath solution increased the amplitude of the outward $K^+$ current which was completely blocked by BKCa[large conductance calcium dependent potassium channels]blocker, IBX[iberiotoxin], and calcium chealator, BAPTA[l,2-bis[o-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid], in whole cell mode. Conclusion : These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.2
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• pp.77-91
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• 2006

Purpose : To address the ability of Dohaekseungkitang (DST: a commonly used herb formulation in Korea, Japan and China to have anti-cancer effect on cervical carcinoma), we investigated the effects of DST on programmed cell death (apoptosis) in HeLa human cervical carcinoma cells. Methods : We cultured HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% CO2. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : After the treatment of DST for 48 hours, apoptosis occurred in a dose-dependent manner. In this study, we have shown that DST induces calpain and the associated caspase-8 and -9 activations. Apoptosis was prevented by pre-incubation of the cells with the calcium cHeLator-BAPTA-AM, calcium channel blocker-Nif edipine or Ryonidine agonist-Ryonidine peptide, implicating calcium in the apoptotic process. Ubiquitous calpains (mu- and m-calpain) have been repeatedly implicated in apoptosis, especially in calcium-related apoptosis. However this study showed 1hat either calpain inhibitor-calpastin or caspase-3 inhibitor-DEVD- did not blocked the herb formulation-induced apoptosis in HeLa human cervical carcinoma cells. D ST initiates a cell death pathway that is partially dependent of caspases. DST-induced apoptosis requires caspase-independent mechanism. Conclusion : We conclude that DST-induced calpain activation triggers the intrinsic apoptotic pathway in which caspase-independent mechanism is also involved.

• Journal of Yeungnam Medical Science
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• v.39 no.4
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• pp.294-299
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• 2022

Background: Medical therapy is the standard treatment for uncomplicated acute type B aortic dissection (ATBAD), but there is little evidence of the need for intensive care unit (ICU) management. Therefore, we aimed to investigate the effects of ICU treatment on uncomplicated ATBAD. Methods: We retrospectively studied patients with uncomplicated ATBAD who were medically treated between January 2010 and July 2020. Patients were divided into short-term ICU stay (SIS) and long-term ICU stay (LIS) groups, according to a 48-hour cutoff of ICU stay duration. The incidence of pneumonia and delirium, rate of aortic events, hospital mortality, and survival rate were compared. Results: Fifty-five patients were treated for uncomplicated ATBAD (n=29 for SIS and n=26 for LIS). The incidence of pneumonia (3.6% vs. 7.7%) and delirium (14.3% vs. 34.6%) was higher in the LIS group than in the SIS group, but the differences were not statistically significant. The survival rates at 1, 3, and 5 years were not different between the two groups (SIS: 96.4%, 92.2%, and 75.5% vs. LIS: 96.2%, 88.0%, and 54.2%, respectively; p=0.102). Multivariate Cox regression analysis for aortic events showed that using a calcium channel blocker lowered the risk of aortic events. Conclusion: Long-term ICU treatment is unlikely to be necessary for the treatment of uncomplicated ATBAD. Active use of antihypertensive agents, such as calcium channel blockers, may be needed during the follow-up period.