• 제목/요약/키워드: Evoked Response

검색결과 250건 처리시간 0.035초

인삼정천탕(人蔘定喘湯)이 호흡기계(呼吸器系)에 미치는 영향(影響) (Effects of Insamjungchuntang on the Respiratory System in Experimental Animals)

  • 김호순;신조영
    • 대한한방내과학회지
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    • 제19권1호
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    • pp.409-427
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    • 1998
  • Insamjungchuntang has been used in Korea for many centuries as a treatment for respiratory disease. The effect of Insamjungchuntang on tracheal smooth muscle is not known. The purpose of the present study is to determine the effect of Insamjungchuntang on histamine and acetylcholine induced tracheal smooth muscle contraction in rats and guinea pigs. Guinea pig (500 g, male) and Sprague Dawley rats (200 g, male) were killed by $CO_2$ exposure and a segment (8-10 mm) of the thoracic trachea from each rat and guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5 g loading tension. The dose of histamine (His) and acetylcholine (Ach) which evoked 50% of maximal response $(ED_{50})$ was obtained from cumulative dose response curves for histamine and acetylcholine$(10^{-7}{\sim}10^{-4}\;M)$. Contractions evoked by His ($ED_{50}$) and Ach $(ED_{50})$ were inhibited significantly by Insamjungchuntang. In guinea pig tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was $38.58\(p<0.05)\;after\;10{\mu}l/ml$ Insamjungchuntang, $90.75\(p<0.01)\;after\;30{\mu}l/ml$. Insamjungchuntang and $133.17\(p<0.01)\;after\;100{\mu}l/ml$ Insamjungchuntang. In rat tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was $10.0\(p<0.05)\;after\;10{\mu}l/ml$ Insamjungchuntang, $80.71\(p<0.01)\;after\;30{\mu}/ml$ Insamjungchuntang and $118.29\(p<0.01)\;after\;100{\mu}l/ml$ Insamjungchuntang. Also, in guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was $45.5\(p<0.01)\;after\;10{\mu}l/ml$ lnsamjungchuntang, and $93.17\(p<0.01)\;after\;30{\mu}l/ml$. lnsamjungchuntang $134.50\(p<0.01)\;after\;100{\mu}l/ml$ Insamjungchuntang. In rat tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was $37.83\(p<0.01)\;after\;10{\mu}l/ml$ lnsamjungchuntang, $90.5\(p<0.01)\;after\;30{\mu}l/ml$ Insamjungchuntang and $135.17\(p<0.01)\;after\;100{\mu}l/ml$ Insamjungchuntang. Propranolol $(10^{-7}\;M)$ slightly but significantly attenuated the inhibitory effects of Insamjungchuntang. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$. Insamjungchuntang fell to 46.42% in guinea pig induced by acetylcholine contraction and by $100{\mu}l/ml$ Insamjungchuntang fell to 5.43% (p<0.05) in rat induced by acetylcholine contraction and the mean percent inhibition caused by $100{\mu}l/ml$ Insamjungchuntang fell to 49.0% in guinea pig induced by histamine contraction and by $100{\mu}l/ml$ Insamjungchuntang fell to 48.6% (p<0.05) in rat induced by histamine contraction. Indomethacin and methylene blue $(10^{-7}\;M)$ did not significantly alter the inhibitory effect of lnsamjungchuntang. Also, I could find the effects of lnsamjungchuntang and Insamjungchuntanggamorphine on the tracheal smooth muscle in guinea pig and rat did not change significantly. These results indicate that Insamjungchuntang can relax histamine and acetylcholine-induced contraction of guinea pig and rat tracheal smooth muscle, and that this inhibition involves sympathetic effects.

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청금탕(淸金湯)의 효능(效能)에 관(關)한 실험적(實驗的) 연구(硏究) (Experimental Studies on the Effects of Chunggeumtang)

  • 김응식;이시형
    • 대한한방내과학회지
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    • 제18권2호
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    • pp.1-26
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    • 1997
  • Chunggeumtang has been used in Korea for many centuries as a treatment for respiratory disease. The effect of Chunggeumtang on tracheal smooth muscle is not konwn. The purpose of the present study is to determine the effect of Chunggeumtang on histamine and acetylcholine induced tracheal smooth muscle contraction in rats and guinea pigs. Guinea pig(500g, male) and Sprague Dawley rats (250g, male) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from each rat and guinea pig was cut into equal swegments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force diplacement transducers under 0.5g loading tension. The dose of histamine (His) and acetylcholine (Ach) which evoked 50% of maximal response ($ED_{50}$) was obtained from cumulative dose response curves for histamine and acetylcholine($10^{-7}{\sim}10^{-4}M$). Contractions evoked by His ($ED_{50}$) and Ach ($ED_{50}$) were inhibited significantly by Chunggeumtang. In guinea pig tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was $6.1%after\;30{\mu}l/ml$ Chunggeumtang, and 49.4% (p<0.01) after $100{\mu}l/ml$ Chunggeumtang. In rat tracheal smooth muscle, the mean percent inhibition of acetylcholine induced contraction was $6.7%\;after\;30{\mu}l/ml$ Chunggeumtang, and $54.2%\;(p<0.01)\;after\;100{\mu}l/ml$ Chunggeumtang. Also, in guinea pig tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was $30.6%\;(p<0.05)\;after\;30{\mu}l/ml$ Chunggeumtang, and $53.0%\;(p<0.01)\;after\;100{\mu}l/ml$ Chunggeumtang. In rat tracheal smooth muscle, the mean percent inhibition of histamine induced contraction was $24.1%\;(p<0.05)\;after\;30{\mu}l/ml$ Chunggeumtang, and $55.3%\;(p<0.01)\;after\;100{\mu}l/ml$ Chunggeumtang. Propranolol and indomethacin($10^{-7}M$) slightly but significantly attenuated the inhibitory effects of Chunggeumtang. Following treatment with propranolol, the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 27.6% in guinea pig induced by acetylcholine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 28.7% (p<0.05) in rat induced by acetylcholine contraction and the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 16.2% in guinea pig induced by histamine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 28.7% (p<0.05) in rat induced by histamine contraction. Indomethacin, the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 20.0% in guinea pig induced by acetylcholine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 16.9% (p<0.05) in rat induced by acetylcholine contraction and the mean percent inhibition caused by $100{\mu}l/ml$ Chunggeumtang fell to 16.4% in guinea pig induced by histamine contraction and by $100{\mu}l/ml$ Chunggeumtang fell to 23.1% (p<0.05) in rat induced by histamine contraction. Methylene blue($10^{-7}M$) did not significantly alter the inhibitory effect of Chunggeumtang. Also, I could find the effects of Chunggeumtang and Chunggeumtanggamorphine on the tracheal smooth muscle in guinea pig and rat did not change significantly. These results indicate that Chunggeumtang can relax histamine and acetylcholine-induced contraction of guinea pig and rat tracheal smooth muscle, and that this inhibition involves sympathetic effects and the release of cyclooxygenase products.

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악하선 선포세포에서 β-아드레날린계 활성화 후 세포내 Ca2+ 농도 증가에 미치는 옥탄올의 효과 (The effect of octanol on the intracellular Ca2+ increase in submandibular acinar cells evoked by β-adrenergic activation)

  • 최정이
    • 치위생과학회지
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    • 제2권1호
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    • pp.47-51
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    • 2002
  • Sprague-Dawley계 흰쥐의 악하선에서 선세포를 분리하여 fura-2/AM(fura-2)으로 염색한 후 spectrofluorometer로 세포내 $Ca^{2+}$농도를 측정하였다. 악하선 세포를 관류장치(perfusion chamber)에 넣고 표준용액을 관류시키면서 isoproterenol($1{\mu}M$)과 octanol(1mM)을 투여한 후 $Ca^{2+}$농도 변화를 측정하였는데 단독 투여시 $Ca^{2+}$농도는 거의 변화하지 않았으나 함께 투여한 경우 세포 내 $Ca^{2+}$농도가 증가함을 확인할 수 있었다. Adenylate-cyclase를 활성화 시키는 forskolin($10{\mu}M$)과 octanol을 함께 투여하였을 때도 isoproterenol의 경우와 유사한 증가 현상을 보이는 것으로 볼 때 octanol과 isoproterenol 또는 forskolin이 함께 작용할 때 세포 내 $Ca^{2+}$가 증가하는 것을 확인할 수 있었다. $Ca^{2+}$의 증가기전을 확인하고자 표준용액의 $Ca^{2+}$를 제거함은 물론 EGTA를 처리하여 세포외부의 $Ca^{2+}$를 제거한 후 상기한 바와 동일한 실험을 반복한 결과 $Ca^{2+}$농도의 증가를 보이지 않았다. 따라서 세포 내 $Ca^{2+}$의 증가는 세포 외부로부터의 $Ca^{2+}$유입 때문인 것으로 확인할 수 있었다. 이러한 $Ca^{2+}$의 유입 capacitative entry pathway를 이용하는지 확인코자 gadolinium($10{\mu}M$)을 처리하였을 때 $Ca^{2+}$농도의 증가가 완전히 억제되지는 않았지만 $Ca^{2+}$의 증가속도와 증가량이 감소되어 있음을 확인할 수 있었다. 이상의 실험결과들을 정리하면 세포 내 $Ca^{2+}$농도의 증가와 관련 ${\beta}$-아드레날린계 관련 약물과 옥탄올(octanol)을 함께 처리할 경우 세포 내 $Ca^{2+}$는 세포 외부에서 유입되어 증가되고 그 경로는 일부 capacitative entry pathway를 통함을 확인할 수 있었다.

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뇌혈류 자가조절에 대한 Endothelium-derived Relaxing Factor의 역할 (Role of Endothelium-derived Relaxing Factor in Cerebral Autoregulation in vivo)

  • 홍기환;유성숙;임병용
    • 대한약리학회지
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    • 제31권1호
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    • pp.27-37
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    • 1995
  • 본 연구에서는 콜린성 기전에 반응하여 분비되는 내피 의존성 이완물질(endothelium-derived relaxing factor, EDRF)나 nitric oxide(NO)가 마취 흰쥐의 뇌혈류 자가조절기전에 관여할 가능성을 관찰하였다. Acetylcholine($10^{-9}-10^{-6}M$)을 포함한 mock 뇌척수액(CSF)을 관류시 뇌연막 동맥은 농도에 의존하여 이완반응 나타내었고(평균; $19.3{\pm}1.7{\mu}m$, n=36), 이러한 이완반응은 $N{\omega}$-nitro-L-arginine(L-NNA, $10^{-5}M$)에 의해서 억제되었을 뿐 아니라 methylene blue($10^{-6}M$)나 oxyhemoglobin($10^{-6}M$)에 의하여도 억제되었다. 한편 이러한 acethlcholine에 의한 뇌연막동맥의 이완반응을 매게하는 무스카린 수용체는 무스카린 수용체 길항제의 봉쇄효과를 관찰한 실험에서 $M_1$$M_3$ 아형으로 생각되었다. L-Arginine을 함유한 mock CSF로 관류시 일어나는 일시적인 혈관이완반응은 NY 83583 ($10^{-5}M$)에 강력히 억제되었으나 L-NNA ($10^{-5}M$)에 의해서는 억제되지 아니하였다. 한편 acetylcholine과 L-arginine에 의한 혈관이완반응은 ATP-sensitive $K^+$ 통로 봉쇄제인 glibenclamide에 의해 유의하게 봉쇄되었다. 나아가 뇌연막동맥의 직경 변화를 동맥압의 변화에 대하여 검정한 결과 혈관이완과 혈관수축의 희귀 직선의 경사도는 $10^{-5}M$ L-NNA의 전처치에 의하여 영향을 받지 아니하였으나, $3{\times}10^{-6}M$ glibenclamide에 의해 유의하게 감소되었다. 이러한 결과로 보아 혈압하강에 대해 쥐의 뇌연막동맥에 나타나는 혈관이완반응은 EDRF(NO)에 의해 매개되지 않는다고 사료된다.

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파낙사디올의 가토적출부신의 카테콜아민 분비작용에 관한 연구 (Studies on Secretion of Catecholamines evoked by Panaxadiol in the Isolated Rabbit Adrenal Gland)

  • 임동윤;박규백;김규형;최철희;배재웅;김무원
    • 대한약리학회지
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    • 제24권1호
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    • pp.31-42
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    • 1988
  • 본 연구에서 한국산 인삼의 활성성분의 하나인 Panaxadiol(PD)에 대한 가토적출부신에서 카테콜아민(CA)의 분비작용과 작용기전을 파악하고자 실험을 시행하여 다음과 같은 결과를 얻었다. $PD(400{\mu}g)$을 가토적출부신에 투여하였을 때 카테콜아민의 분비를 의의있게 증가시켰다. PD의 이러한 CA 분비작용은 atropine 처치로 현저히 억제되었다. Physostigmine 전처치시 PD 뿐만 아니라 Ach의 CA 분비작용은 뚜렷이 증가되었다. 그러나 chlorisondamine 전처치로 PD나 Ach의 분비 효과는 억제되었다. 또한 $PD(400{\mu}g/30\;min)$을 주입한 후에 Ach의 CA 분비 효과는 오히려 강화되었다. PD나 Ach의 작용은 adenosine 전처러시 현저히 증강되었다. EGTA(5mM)와 함께 Ca-free Krebs액으로 30분 주입한 경우에 Ach의 분비작용은 거의 전적으로 차단되었으며, PD의 작용도 약화되었다. 이상의 실험결과로 보아, PD는 가토적출부신에서 $Ca^{++}$ 의존적으로 CA분비를 증가시키며, 이러한 작용은 cholinergi muscarinic 및 nicotinic receptor의 흥분작용에 기인하며, chromaffincell 대한 일부 직접작용도 개재되어 나타나는 것으로 사료된다.

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동방결절 전기적 특성에 대한 $Ca^{2+}$ 효과의 온도에 따른 변화 (Temperature-dependency of $Ca^{2+}$ Effect on the Electrical Activity of Rabbit SA Node)

  • 호원경;김기환;황상익
    • The Korean Journal of Physiology
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    • 제21권1호
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    • pp.1-12
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    • 1987
  • There is evidence that the effect of extracellular $Ca^{2+}$ on heart rate is temperature-dependent: at $38^{\circ}C$ excess $Ca^{2+}$ induces positive chronotropic response, whereas at $30^{\circ}C$ there is no significant chronotropic effect of $Ca^{2+}$. The cause of this temperature-dependency, however, remains still unclear. Therefore, this study was undertaken to investigate the chronotropic effect of external $Ca^{2+}$ at different temperature in the isolated rabbit atria and in the small strips of SA node cut perpendicularly to crista terminalis. In the isolated atria, the $Ca^{2+}$ effect was temperature-dependent: at $35^{\circ}C$ excess $Ca^{2+}$ evoked positive chronotropic response, while at $30^{\circ}C$ there was no significant changes in sinus rate. On the contrary, in the small SA strips external $Ca^{2+}$ induced negative chronotropic effect. At $35^{\circ}C$ changes in $Ca^{2+}$ concentration from 2 to 4, 6, and 10 mM decreased the sinus rate by $2.7{\pm}1.6%$, $11.2{\pm}3.7%$ and $23.2{\pm}8.1%$ respectively. Lowering the temperature to $30^{\circ}C$, the negative chronotropic effect of $Ca^{2+}$ became greater. With intracellular microelectrodes transmembrane potential was recorded in the small SA strips at $30^{\circ}C$, $35^{\circ}C$ and $38^{\circ}C$. As temperature increased from 30 to $38^{\circ}C$, sinus rate was accelerated by $13/min/^{\circ}C$, $APD_{50}$(action ptential duration from peak to 50% repolarization) decreased by $5\;msec/^{\circ}C$, and amplitude of action potential was slightly decreased. With an increase in $Ca^{2+}$ concentrations from 0.5 to 6 mM, overshoot increased and MDP decreased. These $Ca^{2+}$ effects on the overshoot and MDP of action potentials were not altered by temperature. But the $Ca^{2+}$ effects on the rates of diastolic depolarization, systolic depolarization and repolarization were modified by temperature. Discrpancy of the chronotropic effects of $Ca^{2+}$ between isolated atria and small SA strips was discussed.

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마이크로프로세서를 이용한 자동청력검사 시스템 개발 (Development of A-ABR System Using a Microprocessor)

  • 노형욱;이탁형;김남현;김수찬;차은종;김덕원
    • 전자공학회논문지SC
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    • 제46권2호
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    • pp.15-21
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    • 2009
  • 난청은 가장 흔한 선천성 장애이다. 이 질병의 발생 빈도는 신생아 1000명 출생 당 $1{\sim}3$명 정도로 상당히 높다. 이러한 청력 장애가 조기에 발견된다면 수술적인 치료 등으로 예방할 수 있으나, 그렇지 못할 경우 언어와 학습장애를 초래하게 된다. 이런 관점을 근거로 신생아를 대상으로 한 선천성 난청의 선별검사는 큰 의미를 가지며 난청환자의 조기발견을 위한 노력이 필수적이라 할 수 있다. 기존의 수동 청력검사 시스템은 신생아 청력 평가 시 검사자의 주관성에 의존하게 되므로, 청성뇌간 반응의 뇌파 분석이 잘못될 가능성이 커진다. 따라서 본 연구에서는 난청여부를 자동으로 판독하여 결과를 나오도록 개발하고자 하였으며, 또한 기존 제품들과 차별화하기 위하여 휴대용으로 개발하여 차폐실이 아닌 일반 병실에서도 검사가 가능하도록 함에 따라 유소아의 청각 장애를 극복시키는데 기여하고자 하였다.

자극음의 음향적 특성과 청각 뇌간에서의 전기생리학적 반응의 상관성 (Correlation of acoustic features and electrophysiological outcomes of stimuli at the level of auditory brainstem)

  • 전현지;한우재
    • 한국음향학회지
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    • 제35권1호
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    • pp.63-73
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    • 2016
  • 청각기관의 음조체계로 인해 사람들은 일반적으로 주파수 분포에 따라 소리를 듣는다. 그러나 어음인지 측면에서 어음의 음향적 특성이 사람의 뇌에서 어떻게 인식되는지는 여전히 명확하지 않다. 따라서 본 연구에서는 유사한 고주파수 음향적 특성을 갖는 두 개의 어음이 청각 뇌간에서 전기생리학적으로 어떻게 발현되는 지 확인하고자 하였다. 정상 청력을 지닌 20대 성인 33명이 실험에 참여하였다. 자극음으로 두 개의 한국어 단음절 /자/와 /차/, 4개의 주파수로 구성된 톤버스트음(500, 1000, 2000, 4000 Hz)을 사용하여 청성뇌간반응을 얻었다. 연구 결과, 단음절과 톤버스트음 모두 높은 재현성을 보였고, 파형 V는 모든 피검자에게서 잘 발현되었다. 피어슨 상관관계 분석 결과, 3671 ~ 5384 Hz 대역에서 에너지 분포를 갖는 /자/ 음절은 4000 Hz의 톤버스트음과 높은 상관관계를 나타냈다. 그러나 /차/ 음절은 1000 Hz와 2000 Hz의 톤버스트음과 높은 상관성을 보여, 3362~5412 Hz의 음향적 특성과 청각 뇌간에서 생리학적 반응은 일치하지 않았다. 이러한 결과를 바탕으로 사람의 어음인지과정을 면밀히 조사하기 위해 음향-청지각적 매핑후속 연구가 필요하겠다.

$Ca^{2+}$ is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line

  • Park, Soonhong;Ku, Sang Kyun;Ji, Hye Won;Choi, Jong-Hoon;Shin, Dong Min
    • The Korean Journal of Physiology and Pharmacology
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    • 제19권3호
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    • pp.249-255
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    • 2015
  • Wnk kinase maintains cell volume, regulating various transporters such as sodium-chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium-chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and specific conditions is broadly unclear. In the present study, we used a human salivary gland (HSG) cell line as a model and showed that $Ca^{2+}$ may have a role in regulating Wnk kinase in the HSG cell line. Through this study, we found that the HSG cell line expressed molecules participating in the WNK-OSR1-NKCC pathway, such as Wnk1, Wnk4, OSR1, SPAK, and NKCC1. The HSG cell line showed an intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increase in response to hypotonic stimulation, and the response was synchronized with the phosphorylation of OSR1. Interestingly, when we inhibited the hypotonically induced $[Ca^{2+}]_i$ increase with nonspecific $Ca^{2+}$ channel blockers such as 2-aminoethoxydiphenyl borate, gadolinium, and lanthanum, the phosphorylated OSR1 level was also diminished. Moreover, a cyclopiazonic acid-induced passive $[Ca^{2+}]_i$ elevation was evoked by the phosphorylation of OSR1, and the amount of phosphorylated OSR1 decreased when the cells were treated with BAPTA, a $Ca^{2+}$ chelator. Finally, through that process, NKCC1 activity also decreased to maintain the cell volume in the HSG cell line. These results indicate that $Ca^{2+}$ may regulate the WNK-OSR1 pathway and NKCC1 activity in the HSG cell line. This is the first demonstration that indicates upstream $Ca^{2+}$ regulation of the WNK-OSR1 pathway in intact cells.

치과치료용 약물이 치수신경의 반응에 미치는 영향 (EFFECTS OF DENTAL THERAPEUTIC AGENTS ON THE RESPONSE OF THE PULP NERVE)

  • 권오양;윤수한;이종흔
    • Restorative Dentistry and Endodontics
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    • 제15권1호
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    • pp.1-15
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    • 1990
  • The aim of this study was to investigate the effect of dental therapeutic agent on conduction velocity and threshold current of intradental A- and C-fibers in the cat. Inferior alveolar nerve of cat anesthetized with sodium pentobarbital was exposed and dissected until response of functional single pulp nerve until could be evoked by monopolar electrical stimulation of the crown of the lower left canine teeth. 10ms rectangular pulse was used to determine the threshold current and 1ms rectangular pulse was used to determine conduction velocity. After application of calcium chloride (1, 2, 6M), calcium hydroxide mixed with saline, potassium chloride (0.2, 0.8, 1.6M), eugenol, zinc oxide eugenol to the cavity on the labial surface, conduction velocity and threshold current of single pulp nerve unit were compared with the control. In 10 cats, 24 $A{\delta}$- and 11 C- pulp nerve units were recorded. The mean conduction velocities of $A{\delta}$- and C-fibers were 7.5m/sec (SD=5.8) and 1.2m/sec (SD=0.4), respectively. The mean threshold current was $12.3{\mu}A$ (SD=5.3) for $A{\delta}$-fibers and $24.9{\mu}A$ (SD=8.1) for C-fibers. 1, 2, 6M calcium chloride caused decrease of conduction velocity and remarkable increase of threshold current in $A{\delta}$- and C-fibers. The effect of calcium hydroxide mixed with saline was similar but smaller than calcium chloride solution. 0.2M potassium chloride had insignificant effect. In 0.8M potassium chloride, the threshold current was increased although conduction velocity was not affected. In 1.6M potassium chloride, the threshold current was increased and the conduction velocity was slowed down. Spontaneous activity was recorded frequently for first 5 min but gradually reduced both in $A{\delta}$- and C-fibers. Eugenol had irreversible effect on pulp nerve in that initially there were not certain changes in the conduction velocity and threshold current of $A{\delta}$- and C-fibers, but the responses to electrical stimulation were abruptly disappeared after sustained application and were not recovered. Contrary to eugenol, zinc oxide eugenol did not caused significant increase of the threhold current and caused time dependent decrease of the conduction velocity, and did not show any irreversible change.

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