• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.383-388
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• 2015

$K^+$ outward currents in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), were investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) mice of the same age (postnatal day (P) 0-P6) were used as controls. Similar slow rising $K^+$ currents were observed in both genotypes, but their biophysical and pharmacological properties were quite different. The values of Vhalf for activation were significantly different in the heterozygous (+/cir) and homozygous (cir/cir) mice ($-8.1{\pm}2.2mV$, heterozygous (+/cir) mice (n=7) and $-17.2{\pm}4.2mV$, homozygous (cir/cir) mice (n=5)). The inactivation curve was expressed by a single first order Boltzmann equation in the homozygous (cir/cir) mice, while it was expressed by a sum of two first order Boltzmann equations in the heterozygous (+/cir) mice. The $K^+$ current of homozygous (cir/cir) mice was more sensitive to TEA in the 1 to 10 mM range, while the 4-AP sensitivities were not different between the two genotypes. Removal of external $Ca^{2+}$ did not affect the $K^+$ currents in either genotype, indicating that the higher sensitivity of $K^+$ current to TEA in the homozygous (cir/cir) mice was not due to an early expression of $Ca^{2+}$ activated $K^+$ channels. Our results suggest that the $K^+$ outward current of developing homozygous (cir/cir) mice OHCs is different in both biophysical and pharmacological aspects than that of heterozygous (+/cir) mice.

• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.319-325
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• 2015

Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and $12.74{\mu}M$, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.291-297
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• 2011

The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $3.17{\mu}m$ and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.

• The Korean Journal of Physiology and Pharmacology
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• 제12권1호
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• pp.31-35
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• 2008

Lysophosphatidylcholine (LPC), a metabolite of membrane phospholipids by phospholipase $A_2$, has been considered responsible for the development of abnormal vascular reactivity during atherosclerosis. $Ca^{2+}$ influx was shown to be augmented in atherosclerotic artery which might be responsible for abnormal vascular reactivity. However, the mechanism underlying $Ca^{2+}$ influx change in atherosclerotic artery remains undetermined. The purpose of the present study was to examine the effects of LPC on L-type $Ca^{2+}$ current $(I_{Ca(L)})$ activity and to elucidate the mechanism of LPC-induced change of $I_{Ca(L)}$ in rabbit portal vein smooth muscle cells using whole cell patch clamp. Extracellular application of LPC increased $I_{Ca(L)}$ through whole test potentials, and this effect was readily reversed by washout. Steady state voltage dependency of activation or inactivation properties of $I_{Ca(L)}$ was not significantly changed by LPC. Staurosporine (100 nM) or chelerythrine $(3{\mu}M)$, which is a potent inhibitor of PKC, significantly decreased basal $I_{Ca(L)}$, and LPC-induced increase of $I_{Ca(L)}$ was significantly suppressed in the presence of PKC inhibitors. On the other hand, application of PMA, an activator of PKC, increased basal $I_{Ca(L)}$ significantly, and LPC-induced enhancement of $I_{Ca(L)}$ was abolished by pretreatment of the cells with PMA. These findings suggest that LPC increased $I_{Ca(L)}$ in vascular smooth muscle cells by a pathway that involves PKC, and that LPC-induced increase of $I_{Ca(L)}$ might be, at least in part, responsible for increased $Ca^{2+}$ influx in atherosclerotic artery.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.545-553
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• 2020

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K⁺ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC₅₀ value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC₅₀ value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC₅₀ value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

• 한국산학기술학회논문지
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• 제15권10호
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• pp.5945-5949
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• 2014

농촌의 고령화로 인한 일손이 감소되고 있다. 반면 노인들의 일은 늘어나고 있다. 또한 농부들은 대량생산을 목표로 하는 사람들이 늘어나고 있다. 그리고 일 효율의 문제에 있어서도 보완하기 위해 농작물을 보호하는 지지대와 집게에 대한 연구를 하려고 한다. 지지대의 강도는 바람의 세기보다 강하여 파손의 우려는 없지만 집게가 식물을 잡을 만큼의 힘을 가지고 있지 않아서 형상설계 문제로 접근 하였다. 실제 지지대와 집게에 걸리는 하중을 구하고 시뮬레이션 값과 비교하여 시뮬레이션의 정확도를 확인한다. 시뮬레이션의 신뢰성을 토대로 더 큰 힘을 버틸 수 있는 모델과 크기를 선택한다. 본 논문의 연구결과를 통해 0.1N에서 0.6N의 작용력이 작용하여도 1.29N의 작용력까지 버틸 수 있는 농작물 지지대를 설계하여 농작물 고정용 집게에 걸어 고정하게 됨으로 작업시간의 단축과 작물의 생육과 작물의 재해를 방지 및 예방, 도움이 될 것이라 판단된다.

• Journal of Chest Surgery
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• 제22권5호
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• pp.713-723
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• 1989

In order to assess the correlation of the myocardial damage and the duration of cardiopulmonary bypass, measurement of creatine kinase [CK], lactate dehydrogenase [LDH], asparatate aminotransferase [AST], and MB band of CK [CK-MB] were carried out on the first, third, fifth, seventh, and ninth day in 44 patients following open heart surgery [POD 1,3,5,7,9]. And the patients were divided into three groups according to the duration of aortic cross clamp time [ACT]: Group I [ACT< 60 minutes. n=19], Group II [60 minutes < ACT< 90 minutes, n=7] and Group III[90 minutes > ACT, n=18]. 1. The leakage of CK in total patients increased to the highest level at POD 1, with rapid decrease and recovery at POD 7. The leakage of CK in Group III were greater than in Group I from POD 1 to POD 3 [P < 0.01]. The recovery time of CK level was shorter in Group I [POD 3] than in Group II and III [POD 7]. 2. The serum levels of LDH in total patients increased to the highest level at POD 1, with slow recovery until POD 9. The levels of LDH in Group III were higher than in Group I until POD 9 [P < 0.005]. The levels of LDH in Group I and II recovered but not in Group III. 3. The serum levels of AST in total patients increased to the highest level at POD 1, with rapid decrease and recovery at POD 7. The levels of AST in Group III were greater than in Group I from POD 1 to POD 5 [P < 0.05]. The recovery time of AST level was shorter in Group I and II [POD 5] than in Group III [POD 7]. 4. The positive cases for CK-MB in 36 patients were 22 [61.1 %] as a whole, 5[41.6%] in Group I, 4[57.1 %] in Group II, 13[76.4 %] in Group III at POD 1, and a case in each group at POD 3, and only a case in Group Ill at POD 5. It is concluded that the myocardial injury was closely related with the duration of cardiopulmonary bypass in open heart surgery.

• Journal of Chest Surgery
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• 제49권5호
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• pp.356-360
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• 2016

Background: The standard approach in treating cardiac myxoma is the median full sternotomy. With the evolution of surgical techniques, the right minithoracotomy approach has emerged as an alternative method. Since few studies have been published assessing the right minithoracotomy approach, we performed a retrospective study to compare the clinical outcomes of the right minithoracotomy approach with those of the sternotomy approach. Methods: From January 2005 to December 2014, 203 patients underwent resection of a cardiac myxoma. Patients with preexisting cardiac problems were excluded from this study. 146 patients were enrolled in this study; 83 patients were treated using a median sternotomy and 63 patients were treated using a right minithoracotomy. Results: No early mortalities were recorded in either group. Although the cardiopulmonary bypass time and aorta cross-clamp time were significantly shorter in the sternotomy group (p<0.001 and p=0.005), postoperative blood transfusions and arrhythmia events were significantly less common in the thoracotomy group (p=0.004 and p=0.025, respectively). No significant differences were found in the duration of the hospital stay, postoperative intubation time, the duration of the intensive care unit stay, and recurrence. Conclusion: The minimally invasive right minithoracotomy approach is a good alternative method for treating cardiac myxoma because it was found to be associated with a lower incidence of postoperative complications and a shorter postoperative recovery period.

• Molecules and Cells
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• 제37권3호
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• pp.202-212
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• 2014

ClC-1 is a member of a large family of voltage-gated chloride channels, abundantly expressed in human skeletal muscle. Mutations in ClC-1 are associated with myotonia congenita (MC) and result in loss of regulation of membrane excitability in skeletal muscle. We studied the electrophysiological characteristics of six mutants found among Korean MC patients, using patch clamp methods in HEK293 cells. Here, we found that the autosomal dominant mutants S189C and P480S displayed reduced chloride conductances compared to WT. Autosomal recessive mutant M128I did not show a typical rapid deactivation of Cl- currents. While sporadic mutant G523D displayed sustained activation of $Cl^-$ currents in the whole cell traces, the other sporadic mutants, M373L and M609K, demonstrated rapid deactivations. $V_{1/2}$ of these mutants was shifted to more depolarizing potentials. In order to identify potential effects on gating processes, slow and fast gating was analyzed for each mutant. We show that slow gating of the mutants tends to be shifted toward more positive potentials in comparison to WT. Collectively, these six mutants found among Korean patients demonstrated modifications of channel gating behaviors and reduced chloride conductances that likely contribute to the physiologic changes of MC.

• The Korean Journal of Physiology and Pharmacology
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• 제23권6호
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• pp.483-491
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• 2019

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. ${\beta}$-Amyloid ($A{\beta}$) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in $A{\beta}$ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine $A_1$ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the $A{\beta}$ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of $A_1R$ is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.