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A Computational Model of the Temperature-dependent Changes in Firing Patterns in Aplysia Neurons

  • Hyun, Nam-Gyu;Hyun, Kwang-Ho;Hyun, Kwang-Beom;Han, Jin-Hee;Lee, Kyung-Min;Kaang, Bong-Kiun
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.6
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    • pp.371-382
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    • 2011
  • We performed experiments using Aplysia neurons to identify the mechanism underlying the changes in the firing patterns in response to temperature changes. When the temperature was gradually increased from $11^{\circ}C$ to $31^{\circ}C$ the firing patterns changed sequentially from the silent state to beating, doublets, beating-chaos, bursting-chaos, square-wave bursting, and bursting-oscillation patterns. When the temperature was decreased over the same temperature range, these sequential changes in the firing patterns reappeared in reverse order. To simulate this entire range of spiking patterns we modified nonlinear differential equations that Chay and Lee made using temperature-dependent scaling factors. To refine the equations, we also analyzed the spike pattern changes in the presence of potassium channel blockers. Based on the solutions of these equations and potassium channel blocker experiments, we found that, as temperature increases, the maximum value of the potassium channel relaxation time constant, ${\tau}_n(t)$ increases, but the maximum value of the probabilities of openings for activation of the potassium channels, n(t) decreases. Accordingly, the voltage-dependent potassium current is likely to play a leading role in the temperature-dependent changes in the firing patterns in Aplysia neurons.

Phasic and Tonic Inhibition are Maintained Respectively by CaMKII and PKA in the Rat Visual Cortex

  • Joo, Kayoung;Yoon, Shin Hee;Rhie, Duck-Joo;Jang, Hyun-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.6
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    • pp.517-524
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    • 2014
  • Phasic and tonic ${\gamma}$-aminobutyric acidA ($GABA_A$) receptor-mediated inhibition critically regulate neuronal information processing. As these two inhibitory modalities have distinctive features in their receptor composition, subcellular localization of receptors, and the timing of receptor activation, it has been thought that they might exert distinct roles, if not completely separable, in the regulation of neuronal function. Inhibition should be maintained and regulated depending on changes in network activity, since maintenance of excitation-inhibition balance is essential for proper functioning of the nervous system. In the present study, we investigated how phasic and tonic inhibition are maintained and regulated by different signaling cascades. Inhibitory postsynaptic currents were measured as either electrically evoked events or spontaneous events to investigate regulation of phasic inhibition in layer 2/3 pyramidal neurons of the rat visual cortex. Tonic inhibition was assessed as changes in holding currents by the application of the $GABA_A$ receptor blocker bicuculline. Basal tone of phasic inhibition was maintained by intracellular $Ca^{2+}$ and $Ca^{2+}$/calmodulin-dependent protein kinase II (CaMKII). However, maintenance of tonic inhibition relied on protein kinase A activity. Depolarization of membrane potential (5 min of 0 mV holding) potentiated phasic inhibition via $Ca^{2+}$ and CaMKII but tonic inhibition was not affected. Thus, phasic and tonic inhibition seem to be independently maintained and regulated by different signaling cascades in the same cell. These results suggest that neuromodulatory signals might differentially regulate phasic and tonic inhibition in response to changes in brain states.

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

  • Kim, Young-Hwan;Ahn, Duck-Sun;Joeng, Ji-Hyun;Chung, Seungsoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.6
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    • pp.489-495
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    • 2014
  • Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ${\omega}$-conotoxin GVIA (CgTx), a selective N-type $Ca^{2+}$ channel ($I_{Ca-N}$) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ${\omega}$-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of $I_{Ca-N}$ which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

Nifedipine Enhances Vasodepressor and Natriuretic Responses to Atrial Natriuretic Peptide in Anesthetized Rats (Nifedipine이 Atrial Natriuretic Peptide의 혈압내림효과에 미치는 영향)

  • Lee, Jong-Eun;Choi, Ki-Chul
    • The Korean Journal of Physiology
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    • v.24 no.1
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    • pp.115-121
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    • 1990
  • The interaction between a calcium channel blocker nifedipine and atrial natriuretic peptide (ANP) was examined in normotensive and renal hypertensive rats. The infusion of either ANP or nifedipine produced a significant decrease in mean arterial pressure (MAP). The combined infusion of ANP with nifedipine resulted in a greater fall of MAP than did the infusion of each drug alone. ANP significantly increased urinary volume and excretion of sodium, while nifedipine was without effects. The diuretic/natriuretic effects of ANP were potentiated by the combined infusion with nifedipine. The vasodepressor and renal effects of ANP or nifedipine were qualitatively similar between the normotensive and hypertensive rats. Nifedipine caused an upward and leftward shift of the ANP dose-relaxation curve of the phenylephrine-precontracted thoracic aortic rings isolated from the normotensive rats , suggesting that the vasodilation sensitivity to ANP is increased in the presence of nifedipine. These results indicate that nifedipine enhances the vasodepressor effect of ANP, the likely mechanisms being attributable to a contraction of effective intravascular volume as a consequence of potentiated renal excretion and a greater peripheral vasodilation.

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A Case of Supravalvular Pulmonic Stenosis in a Maltese Dog (말티즈견에서 발생한 판막상형 폐동맥판 협착증 증례)

  • Kim, Seong-Jun;Kang, Min-Hee;Kim, Su-Chan;Choi, Young-Chul;Kim, Seung-Gon;Lee, Chang-Min;Jung, Da-Min;Park, Hee-Myung
    • Journal of Veterinary Clinics
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    • v.31 no.4
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    • pp.325-328
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    • 2014
  • A 8-month-old female Maltese dog was presented with a history of heart murmur. In physical examination, grade 4/6 systolic murmur heard at the left heart base. Electrocardiography showed sinus arrhythmia, right axis deviation, deep S wave and splintered QRS complex. Thoracic radiography revealed enlarged right side heart and bulging of the main pulmonary artery. Echocardiography showed mild hypertrophy of right ventricle, a supravalvular stenosis, marked post-stenotic dilation of the main pulmonary artery and a moderately increased pulmonary arterial velocity through the stenotic area (4.4 m/s, pressure gradient of 78.7 mmHg). The dog was diagnosed with supravalvular pulmonic stenosis based on the diagnostic imaging findings. Medical management using ${\beta}1$-blocker and ACE inhibitor was started in this dog and this is first case report described diagnostic characteristic features of supravalvular pulmonic stenosis in korea.

Mechanisms of tert-Buthyl Hydroperoxide-induced Membrane Depolarization in Rat Spinal Substantia Gelatinosa Neurons

  • Lim, Seong-Jun;Chun, Sang-Woo
    • International Journal of Oral Biology
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    • v.33 no.3
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    • pp.117-123
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    • 2008
  • Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In the present study, whole cell patch clamp recordings were carried out to investigate the effects of tert-buthyl hydroperoxide (t-BuOOH), an ROS, on neuronal excitability and the mechanisms underlying changes of membrane excitability. In current clamp condition, application of t-BuOOH caused a reversible membrane depolarization and firing activity in substantia gelatinosa (SG) neurons. When slices were pretreated with phenyl-N-tert-buthylnitrone (PBN) and ascorbate, ROS scavengers, t-BuOOH failed to induce membrane depolarization. However, isoascorbate did not prevent t-BuOOH-induced depolarization, suggesting that the site of ROS action is intracellular. The t-BuOOH-induced depolarization was not blocked by pretreatment with dithiothreitol (DTT), a sulfhydryl-reducing agent. The membrane-impermeant thiol oxidant 5,5-dithiobis 2-nitrobenzoic acid (DTNB) failed to induce membrane depolarization, suggesting that the changes of neuronal excitability by t-BuOOH are not caused by the modification of extrathiol group. The t-BuOOH-induced depolarization was suppressed by the phospholipase C (PLC) blocker U-73122 and inositol triphosphate ($IP_3$) receptor antagonist 2-aminoethoxydiphenylbolate (APB), and after depletion of intracellular $Ca^{2+}$ pool by thapsigargin. These data suggest that ROS generated by peripheral nerve injury can induce central sensitization in spinal cord, and t-BuOOH-induced depolarization may be regulated by intracellular $Ca^{2+}$ store mainly via $PLC-IP_3$ pathway.

β-Adrenergic Receptors : New Target in Breast Cancer

  • Wang, Ting;Li, Yu;Lu, Hai-Ling;Meng, Qing-Wei;Cai, Li;Chen, Xue-Song
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8031-8039
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    • 2016
  • Background: Preclinical studies have demonstrated that ${\beta}$-adrenergic receptor antagonists could improve the prognosis of breast cancer. However, the conclusions of clinical and pharmacoepidemiological studies have been inconsistent. This review was conducted to re-assess the relationship between beta-adrenoceptor blockers and breast cancer prognosis. Materials and Methods: The literature was searched from PubMed, EMBASE and Web of Nature (Thompson Reuters) databases through using key terms, such as breast cancer and beta-adrenoceptor blockers. Results: Ten publications met the inclusion criteria. Six suggested that receiving beta-adrenoceptor blockers reduced the risk of breast cancer-specific mortality, and three of them had statistical significance (hazard ratio (HR)=0.42; 95% CI=0.18-0.97; p=0.042). Two studies reported that risk of recurrence and distant metastasis (DM) were both significantly reduced. One study demonstrated that the risk of relapse-free survival (RFS) was raised significantly with beta-blockers (BBS) (HR= 0.30; 95% CI=0.10-0.87; p=0.027). One reported longer disease-free interval (Log Rank (LR)=6.658; p=0.011) in BBS users, but there was no significant association between overall survival (OS) and BBS (HR= 0.35; 95% CI=0.12-1.0; p=0.05) in five studies. Conclusions: Through careful consideration, it is suggested that beta-adrenoceptor blockers use may be associated with improved prognosis in breast cancer patients. Nevertheless, larger size studies are needed to further explore the relationship between beta-blocker drug use and breast cancer prognosis.

SIADH Caused by the Synergistic Effect of S-1 and Thiazide (S-1과 티아지드 상승효과에 의한 항이뇨호르몬과다분비증후군 1예)

  • Ha, Tae-Kyung;Kwon, Sung-Joon
    • Journal of Gastric Cancer
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    • v.6 no.3
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    • pp.198-201
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    • 2006
  • Hyponatremia is a dangerous electrolyte disturbance in patients on chemotherapy and may cause sudden death if not detected early. SIADH (syndrome of inappropriate antidiuretic hormone) is one of the known causes of hyponatremia in patients undergoing chemotherapy. Few chemotherapeutic agents, however, are reported to cause SIADH. The current study reports that SIADH developed in a 55 year old woman on S-1 ($80\;mg/m^{2}$) and cisplatin ($60\;mg/m^{2}$) chemotherapy for the peritoneal metastasis of gastric cancer. The patient underwent a total gastrectomy, a splenectomy, and a segmental resection of the transverse colon for gastric cancer. She had used thiazide and ${\beta}-blocker$ to treat hyperiension for 12 years. She admitted to our hospital with complaining of general weakness, dysarthria, loss of appetite, and urinary discomfort. The serum level of sodium and potassium were 94 mEq/L and 2.2 mEq/L respectively. The hyponatremia completely resolved uneventfully after 3% saline infusion, which led to normalized electrolyte balance. The patient was discharged on the 13th hospital day.

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A Study on Performance Evaluation and Security Methods of u-IT Electrical Safety Integrated Management System's Module (u-IT 전기안전통합관리시스템의 모듈별 성능평가와 보안방법 연구)

  • Park, Dae-Woo;Kim, Eung-Sik;Choi, Choung-Moon
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.14 no.6
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    • pp.1447-1452
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    • 2010
  • Ubiquitous society to build basic infrastructure in the power supply and power equipment safety is important. u-City in order to prevent the disaster of u-IT Power Equipment Performance Module and the security for the safety of the u-City is necessary. In this paper, the power unit of u-IT module, temperature sensor, humidity sensor, equipped with sensors arranged throughout the fire, and home distribution boards, Home Network Wall-Pad, Blocker, MPNP black boxes, arc detection, arc safety equipment, outlet of the modular performance evaluation methods and security methods will be studied. u-IT power devices and sensors to analyze the information conveyed by proactive risk and ensure safety, access control, authentication, security safeguards, such as u-IT integrated management system for electrical safety and strengthen the security, safety and security with a u-City will contribute to the construction and operation.

Display Types for Alleviating Negative Attitude toward Advertisements Attached to Web Articles (인터넷 신문기사에 첨부된 광고의 거부감 경감을 위한 광고 제시 방식)

  • Yu, Hyun-Jin;Lim, Seong-Taek;Chung, Jin-Gu;Lee, Ju-Hwan
    • 한국HCI학회:학술대회논문집
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    • 2007.02b
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    • pp.554-559
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    • 2007
  • 최근 인터넷 관련 기술의 급속한 발전으로 사람들의 다양한 사회적, 경제적 행위들이 인터넷을 기반으로 확대되고 있다. 특히 우리나라의 경우 초고속 통신망의 확산과 더불어 인터넷 쇼핑몰과 상거래시장 또한 빠르게 성장하였다. 이러한 상황에서 인터넷을 매체로 하는 광고기법 또한 다양하게 적용되고 있는데, 인터넷을 통한 광고 효과를 극대화하기 위해 인터넷 신문기사 주변에 배치된 배너광고, 팝업광고 등 여러 가지 시도들이 있어왔다. 이러한 시도들은 인터넷 사용자의 편의에 대한 고려보다는 광고내용을 얼마나 잘 전달할 수 있는가에 초점이 맞추어져 있었다. 그러나 광고내용이 잘 전달된다 하더라도 소비자가 그 광고에 대해 불쾌감을 느끼게 된다면 과연 인터넷 광고효과가 높다고 말할 수 없을 것이다. 예를 들어, 팝업광고에 대한 대응책으로 개인적으로 팝업 블록커(pop-up blocker)를 사용하겠는가에 대한 설문조사 결과를 보면 사람들이 팝업 블록커를 이용해서라도 팝업광고를 피하고자 하는 비율이 77%에 달한다는 것을 알 수 있다. 실제로 Windows XP 서비스팩 2 이후의 버전은 인터넷 사용자들의 편의를 위해 자동 팝업 차단기능을 갖추고 있는 실정이다. 팝업광고를 통해 아무리 높은 정보전달 효과가 발생한다 하더라도 사용자들은 팝업광고에 대하여 거부감이나 부정적 감정을 느낄 수 있다. 그리고 광고정보가 전달된다 하더라도 팝업광고에 대한 사용자들의 불편함이 그 광고에 대한 부정적 감정으로 전이되어 광고대상에 대한 이미지에 악영향을 미칠 수 있음에 유의해야 한다. 그러므로 광고효과는 극대화하면서, 혹은 기존의 수준을 유지하면서 광고에 대한 거부감을 줄인 광고형태를 찾기 위한 다양한 노력들이 필요하다. 이를 위해 본 연구에서는 인터넷 신문기사에 첨부된 광고에 대한 사용자의 거부감을 줄일 수 있는 새로운 광고 제시 방식을 찾고자 일반적으로 사용되는 배너와 팝업 등 두 가지 광고 제시 방식과 전면에 돌출하지 않는 형태로 인터넷 신문기사의 배경에 삽입된 광고 제시 방식을 비교하였다. 그 결과, 인터넷 신문기사 영역의 주변 특정 부분(코너나 중간 부분 등)에 광고를 삽입한 배너 형태의 광고와 인터넷 신문기사 위에 광고가 돌출 등장하여 콘텐츠를 가리는 팝업 형태의 광고 제시 방식보다 새롭게 제안된 백그라운드 형태의 광고 제시 방식이 인터넷 신문기사를 읽는 사용자에게 거부감을 줄이며 동시에 광고효과를 유지할 수 있음을 확인하였다. 이러한 결과를 인터넷 광고 제시 방식으로 활용한다면 인터넷 사용자에게 콘텐츠를 방해하여 발생하는 명시적인 거부감(explicit negative attitude)을 줄이면서도 암묵적인(implicit) 광고효과를 얻을 수 있을 것이다.

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