• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.171-177
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• 2011

Tonic smooth muscle exhibit the latch phenomenon: high force at low myosin regulatory light chains (MRLC) phosphorylation, shortening velocity (Vo), and energy consumption. However, the kinetics of MRLC phosphorylation and cellular activation in phasic smooth muscle are unknown. The present study was to determine whether $Ca^{2+}$-stimulated MRLC phosphorylation could suffice to explain the agonist- or high $K^+$-induced contraction in a fast, phasic smooth muscle. We measured myoplasmic [$Ca^{2+}$], MRLC phosphorylation, half-time after step-shortening (a measure of Vo) and contractile stress in rabbit urinary bladder strips. High $K^+$-induced contractions were phasic at both $22^{\circ}C$ and $37^{\circ}C$: myoplasmic [$Ca^{2+}$], MRLC phosphorylation, 1/half-time, and contractile stress increased transiently and then all decreased to intermediate values. Carbachol (CCh)-induced contractions exhibited latch at $37^{\circ}C$: stress was maintained at high levels despite decreasing myoplasmic [$Ca^{2+}$], MRLC phosphorylation, and 1/half-time. At $22^{\circ}C$ CCh induced sustained elevations in all parameters. 1/half-time depended on both myoplasmic [$Ca^{2+}$] and MRLC phosphorylation. The steady-state dependence of stress on MRLC phosphorylation was very steep at $37^{\circ}C$ in the CCh- or $K^+$-depolarized tissue and reduced temperature flattend the dependence of stress on MRLC phosphorylation compared to $37^{\circ}C$. These data suggest that phasic smooth muscle also exhibits latch behavior and latch is less prominent at lower temperature.

• 대한약리학회지
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• 제13권2호
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• pp.1-9
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• 1977

최근 강심작용 약물로 보고된 부자 부타놀 분획의 가토 심방근에서의 자극빈도에 따른 강심효과를 분석한 결과는 다음과 같다. 1) 가토 심방근의 수축력은 자극빈도에 따라 polyphasic한 수축양상을 보였으며 rested-state contraction은 $120{\sim}400sec$의 interval에서 나타났으며 이후 10sec의 간격까지는 급격한 수축력의 감소를 보이는, 축적NIEA가 PIEA의 양을 능가하는 양상을 보였으며 이 이하의 자극 빈도에서는 수축력의 증가를 보였고 대부분 0.25 sec이하의 빈도의 자극으로는 수축력의 감소를 보였다. 2) Ouabain은 저 농도에서는 interval-strength curve에 대하여 rested-state contraction의 증가와 전 자극빈도에서 비슷한 수축력의 증가를 나타내었으며, 고농도에서는 rested-state contraction의 증가와 축적 NIEA의 소멸 속도를 증가시켰으나 이는 rested-state contraction을 나타내는 시간의 단축에 따른 이차적 효과로 판정하였다. 또한 ouabain 자극빈도에 따른 강심 효과의 양상은 세포외 calcium 농도를 증가시킨 때와 유사한 양상이었다. 3) Norepinerhrine은, rested-state contraction에는 거의 영향을 주지 않았으며, 고 빈도에서 더욱 현저한 강심 작용을 나타내었고 축적 PIEA의 양의 증가와 매 beat 당 산출하는 PIEA의 양의 증가를 나타내었다. 4) 부자 부타놀 분획은 norepinephrine과 유사하고 빈도에서 수축력의 증가가 현저 하였으며, 수축력의 증가는 용량 반응 상관을 보였으며, PIEA 축적량 및 매 beat 당 산출하는 PIEA를 증가 시켰다. 따라서 고빈도에서의 강력한 수축력의 증가는 PIEA에 대한 효과에 의할 것으로 사료하였다.

• 대한수의학회지
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• 제35권2호
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• pp.245-254
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• 1995

The density of ATP-sensitive potassium($K_{APT}$) channels, that open as intracellular ATP concentration falls below a critical level, is very high in skeletal muscle surface membrane and those high density may imply that $K_{ATP}$ channels have very important physiological roles. To elucidate a role of $K_{ATP}$ in relation to fatigue, the modulating effects of potassium channel openers and blockers on the fatigue velocity(FV) of mouse extensor hallucis longus muscle(EHL) were investigated in vitro. Twitch contraction was induced by an electrical field stimulation (EFS: 24-48V, 20ms, 0.2-4Hz) and resulting contraction force was isometrically recorded. The twitch forces were gradually decreased to 25% of initial contraction force(ICF) in $37.52{\pm}1.55sec$($mean{\pm}s.e.m.$, n=135), indicating the fatigue phenomena. The mean velocity for development of the fatigue was measured during the period that twitch force decreased to half($FV_{0/0.5}$) and during the period from half to 25%($FV_{0.5/0.25}$) of ICF. The fatigue was induced once every one hour and the tissue response was stable for up to 4 hours. In control condition, ICF was $5.8{\pm}0.12g$ (n=144) and decreased to 50% of ICF with the mean fatigue velocity of $0.182{\pm}0.006g/sec$($FV_{0/0.5}$, n=135) and from 50% to 25% of ICF with $0.084{\pm}0.004g/sec$($FV_{0.5/0.25}$, n=135). Cromakalim($50{\mu}M$) significantly increased $FV_{0.5/0.25}$(n=4). Glibenclamide($IC_{50}>50{\mu}M$), $Ba^{2+}$($IC_{50}=10{\mu}M$), 4-aminopyridine($FV_{0/0.5}$, $IC_{50}=0.5mM$; $FV_{0.5/0.25}$, $IC_{50}=2mM$) decreased both $FV_{0/0.5}$ and $FV_{0.5/0.25}$ concentration-dependently up to 75%. $TEA^+$(30mM), E-4031($10{\mu}M$), tolbutamide(1mM) decreased $FV_{0.5/0.25}$, but apamin(300nM) and $TEA^+$(10mM) showed no significant effects. Our results suggest that activation of the $K_{ATP}$ channels may be major cause of $K^+$ outflux during development of the fatigue and the isolated EHL muscle could be an useful experimental preparation in studying the fatigue phenomena in skeletal muscle. In addition, the possibility of activation of delayed rectifier during the fatigue development remains to be studied further.

• 동의생리병리학회지
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• 제20권6호
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• pp.1620-1624
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• 2006

This study was performed to investigate a vasodilatory efficacy and its underlying mechanisms of the mixture of Cnidium officinale, Petasites japonicus and Coptis chinensis (CPC), CPC relaxed rat aortic vascular strips in endothelium-independant manner precontracted with phenylephrine or KCI(50mM), but the magnitude of relaxation was greater in KCI induced contraction. L-NAME, iNOS inhibitor, and methylen blue(MB), cGMP inhibitor, did not attenuate the relaxation responses of CPC. Furthermore, the contraction by increaseing $Ca^{2+}$ concentration (0.3-10.0mM) to a $Ca^{2+}$-free high $K^+$ (60mM) was significantly reduced by CPC pretreatment. These results suggest that the relaxation effect of CPC is related with the block of $Ca^{2+}$ influx via $Ca^{2+}$ channel.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.31-41
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• 1986

The sufficient myoplasmic $Ca^{++}$ to react with the contractile proteins is necessary to induce contraction of a cardiac muscle. These $Ca^{++}$ for the production of muscle contraction are supplied from the three recognized $Ca^{++}$ sources; internal $Ca^{++}$ release via the sarcoplasmic reticulum(SR), $Ca^{++}$ influx through a gated Ca-channel in the membrane as a Isi, and $Ca^{++}$ transport by the mechanism of Na/ca exchange. However, it is still controversial which $Ca^{++}$ sources act as a main contributor for myoplasmic $Ca^{++}$, Therefore, this study was undertaken in order to examine the $Ca^{++}$ sources for the contraction of frog ventricle. There is evidence that the SR is sparse in frog ventricular fibers, and that T-tubules are absent. Isolated ventricular strips of frog, Rana nigromaculata, were used in this experiment. Isometric tension was recorded by force transducer, and membrane potentials of ventricular muscles were measured through the intracellular glass microelectrodes, which were filled with 3M KCI and had resistance of $30{\pm}50M{\Omega}$. All experiments were performed at room temperature in a tris·buffered Ringer solution which was aerated with 100% $O_2$. Isotonic high K, low Na solution was used to induce K-contracture, K-contracture appeared at the concentration of 20 to 30mM-KCI and was potentiated in parallel with the increase in KCI concentration. The contracture had two components: an initial rapid phasic and a subsequent slow tonic contractile responses. Membrane Potentials measured at normal Ringer solution(2.5mM KCI) was -90 to -100 mV, and decreased linearly as the KCI concentration increased; -55mV at 20mM.KCI, -45mV at 30 mM.KCI, -30 mY at 50 mM.KCI, and -12 mV at 100 mM.KCI. K-contracture was evoked firstly at the membrane potential of -45 mV. The contracture was potentiated by the increase of bathing extracellular $Ca^{++}$ concentration. However, in the absence of $Ca^{++}$ the contracture was almost not induced by 50 mM.KCI solution. Caffeine(20mM) in normal Ringer solution, which is known to release $Ca^{++}$ from SR without substantial effects on the $Ca^{++}$ fluxes across the surface membrane, did not affect membrane potential and also not initiate contracture, but the caffeine in 20 mM-KCI Ringer solution produced a contracture. Above results suggest that the main $Ca^{++}$ source for the K·contracture of frog ventricle is $Ca^{++}$ influx through the voltage-dependent Ca-channel, and that in the K-contracture at the concentration of 100 mM-KCI, the mechanism of Na/ca exchange also partly contributs, in addition to the $Ca^{++}$ influx.

• 약학회지
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• 제37권4호
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• pp.397-407
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• 1993

The muscarinic antagonist l-[benzilic-4,4'-$^3H$]quinuclidinyl benzilate([$^3H$]QNB) bound to a single class of muscarinic receptor with high affinity in guinea pig ileal membranes. The $K_{D}$ and B$_{max}$ values for [$^3H$]QNB calculated from analysis of saturation isotherms were 54 pM and 156fmol/mg, respectively. H$_{1}$-blockers inhibited [$^3H$]QNB binding to ileal membranes with $K_{i}$ values ranged from 0.008 $\mu{M}$ to 1.6 $\mu{M}$. The pseudo-Hill coefficients of H$_{1}$-blockers for inhibition of [$^3H$]QNB binding to the ileal membranes were close to unit. The $K_{i}$ values for H$_{1}$-blockers were similar to the $K_{M}$ values calculated by Schild plot of functional data obtained from inhibition of the carbachol-induced contraction in guinea-pig ileum, suggesting that binding of H$_{1}$-blockers vs [$^3H$]QNB in ileal membranes represents an interaction with a receptor of physiological relevance. The $K_{H}$ values of H$_{1}$-blockers for H$_{1}$-receptor estimated from inhibition of the histamine-induced contraction were the range of 0.15 nM to 56.5 nM. The $K_{M}$/K$_{H}$ ratio of H$_{1}$-blockers varied over a wide range of 3 to 2300. Thus, the antihistaminic potencies of H$_{1}$-blockers do not correlate with their antimuscarinic potencies, which suggest that antihistamines have different antimuscarinic potencies in therapeutic blood levels causing similar antiallergic effect. Among 13 traditional antihistaminics examined in this study, drug having the highest and the lowest $K_{M}$/K$_{H}$ ratio is triprolidine and diphenidol, respectively. The present results demonstrate that the antimuscarinic property of antihistamines is not necessary for their antiallergic effect, and data on the affinity of antihistamines for muscarinic and H$_{1}$-receptors can be an important parameter in the selection and evaluation of these drugs.

• 대한약리학회지
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• 제16권1호
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• pp.35-39
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• 1980

In this study, the effects of phenoxybenzamine and related drugs on the action of CCK-PZ and caerulein were examined in isolated gall bladder of guinea pig and higher esophagus strip of fowl. The strips were placed in a bath containing Locke-Ringer solution maintained at $38^{\circ}C$. Oxygen was continuously bubbled through the solution. The contractile response was measured isometrically by a force displacement transducer connected to polygraph. In isolated gall bladder preparation caerulein produced contractile response of CCK-PZ type, but the relative potency on a weight basis was 30 times stronger than CCK-PZ. The response of caerulein or CCK-PZ was not blocked by cholinergic blocking agent and both alpha and beta adrenergic blockades, however, the response of caerulein or CCK-PZ was exceptionally blocked by phenoxybenzamine. In isolated esophagus strip CCK-PZ with high concentration produced marked contraction which was not modified by atropine and other blocking agents, whereas the response was blocked by phenoxybenzamine. These results lead to the conclusion that phenoxybenzamine inherently inhibits the contractile response of CCK-PZ and caerulein on esophagus and other smooth muscle.

• Journal of Microbiology and Biotechnology
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• 제11권1호
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• pp.138-142
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• 2001

During the course of searching for anti-allergic substances from unexplored plant sources, an inhibitor of leukotriene $D_4$-induced tracheal contraction was isolated from Euphoribia helioscopia. This isolated polyphenol compound, known as helioscopinin-A, showed a certain inhibitory activity on capillary permeability in passive cutaneous anaphylaxis responses of rats and also on antigen-induced bronchial constriction in an experimental asthma model of guinea pigs. The compound at a high concentration weakly inhibited histamine release from isolated mast cells of rats. It is suggested that this compound is an anti-allergic and anti-asthmatic which exerts its activity through antagonism on leukotrene $D_4$-induced responses. A partial inhibition of allergic mediator relase may also bee involved.

• 한국초전도저온공학회:학술대회논문집
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• 한국초전도저온공학회 2002년도 학술대회 논문집
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• pp.27-30
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• 2002

The particle velocity in superfluid helium (He II) induced by a gas dynamic shock wave impingement onto He II free surface were studied experimentally by using Schlieren visualization method with an ultra-high speed video camera. It is found form visualization results that a dark zone in the immediate vicinity of the vapor-He II interface region is formed because of the high compressibility of He II and is developed toward bulk He II with the flowing-down speed of the vapor-He II interface. The mass velocity behind a transmitted compression shock wave that is equal to the contraction speed of He II amounts to 10 m/sec, the Reynolds number of which reaches $10^{7}$. This fact suggests that the superfluid shock tube facility can be applied to an experimental facility for high Reynols number flow as an alternative to the superfluid wind tunnel.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.705-714
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• 1998

Cerebral blood vessels relax when extracellular $K^+$ concentrations $([K^+])_e$ are elevated moderately $(2{\sim}15$ mM, $K^+-induced$ vasorelaxation). We have therefore studied the underlying mechanism for this $K^+-induced$ vasorelaxation in the isolated middle cerebral arteries (MCAs). The effects of ouabain and $Ba^{2+}\;on\;K^+-induced$ vasorelaxation were examined to determine the role of sodium pump and/or Ba-sensitive process (possibly, inward rectifier K current) in the mechanism. Mulvany myograph was used to study 24 rats, 18 rabbits, and 10 humans MCAs $(216{\pm}3\;{\mu}m,\;347{\pm}7\;{\mu}m,\;and\;597{\pm}39\;{\mu}m$ in diameter when stretched to a tension equivalent to 55 mmHg). High $K^+$ (125 mM) and $PGF_{2{\alpha}}\;(1{\sim}10\;{\mu}M)$ induced concentration-dependent contractions in all 3 species, while histamine $(10{\sim}50\;{\mu}M)$ evoked contraction only in the rabbits and induced relaxation in the rats and humans. Addition of $K^+\;(2{\sim}10\;{\mu}M)$ to the control solution induced vasorelaxations. These effects were inhibited by the pretreatment with both ouabain $(10\;{\mu}M)$ and $Ba^{2+}\;(0.1{\sim}0.3\;mM)$ in the rat, but only with ouabain $(10\;{\mu}M)$ in the rabbit and human. These results suggest that $K^+-induced$ vasorelaxation occurs via the stimulation of electrogenic Na pump in the rabbit and human MCAs, while in the rat MCAs via the activation of both Na pump and Ba-sensitive process.