Preceding Stimulus Frequency-Dependent Potentiation of the Postrest Shortening of the Action Potential Duration in Rabbits.
Naohiko TakahashiMorio ItoShuji IshidaTakao FujinoMikiko NakagawaHidetoshi YonemochiTetsu IwaoTatsuhiko OoieMasahide HaraTetsunori SaikawaToshiie Sakata
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Action potential duration (APD) in rabbit ventricular myocardium shortens after a rest period (postrest shortening). However, the effects of preceding stimulus frequency on the postrest shortening have not been elucidated. We recorded transmembrane action potentials (TAPs) and monophasic action potentials (MAPs) from the rabbit ventricle. In in vitro experiments, repetitive regular stimuli (S1) at cycle lengths ranging between 500 to 3000 ms were followed by a single extrastimulus (S2) at a coupling interval of 5000 ms. A decrease in S1S1 interval resulted in a progressive shortening of the duration of TAP (TAPD) elicited by S2 (S2-TAPD), which was potentiated by increasing extracellular calcium concentration ([Ca2+] o) or application of ouabain and was inhibited by lowering [Ca 2+]o or verapamil. Application of ryanodine was most effective in lengthening S2-TAPD following a short S1S1 interval. 4-aminopyridine and E4031 caused marked lengthening of S2-TAPD when S1S1 was long. However, the lengthening effect was attenuated and disappeared with a shorter S1S1 interval. In in vivo experiments, regular ventricular pacing (S1) at cycle lengths ranging between 250 to 1000 ms was followed by a single extrastimulus (S2) with a coupling interval (S1S2) of 1500 ms. A decrease in the S1S1 interval also resulted in progressive shortening of the duration of MAP elicited by S2. Our results indicate that the postrest shortening is potentiated by an increase in the preceding stimulus frequency in the rabbit ventricle, in which the function of sarcoplasmic reticulum may play a significant role.Keywords:
Stimulus (psychology)
The effect of ouabain (10(-5) M) on the Ca2+-evoked phasic contraction was examined in various depolarized vas deferens of the guinea-pig. Ouabain-induced potentiation of the contraction occurred in muscle depolarized with 40 mM K+, but not in muscle depolarized with 0 mM or 137 mM K+. Furthermore, this potentiating effect of ouabain was investigated in the presence of Mn2+ and Mg2+, each of which has an inhibitory effect on Ca2+-contraction. It was strongly inhibited by Mn2+, but unaffected by Mg2+. From these findings it is suggested that ouabain facilitates Ca2+-entry, which is accompanied by the spike generation.
Vas deferens
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瞄准：在人的阴茎海绵体在试管内上评估 verapamil 的弛缓的效果并且为可勃起的机能障碍(编辑) 作为一个处理估计这药的潜力。方法：人的阴茎海绵体的准备从最近被获得有正常的死亡的年轻人可勃起的功能。当 10 micromol/L 脱羟肾上腺素导致的收缩被 verapamil 或车辆控制(无菌的水) 的不同剂量减少时，等轴的紧张和详细曲线被记录。人的阴茎海绵体准备的紧张在增加 verapamil 或车辆前被描述为他们的最高的紧张的一个百分比。ANOVA 和最少的有效差量测试被用于统计分析。结果：1 micromol/L， 10 micromol/L 和 100 micromol/L verapamil 的剂量导致了松驰(35.28+/-7.96 )% ，(55.91+/-6.41 )% ，(85.68+/-4.16 ) 在 30 min 以后的 % 分别地。车辆控制同时削尖生产松驰(-0.06+/-10.57)%(P<0.05 ) 。结论：Verapamil 在放松脱羟肾上腺素在试管内导致的正常人的语料库多孔的平滑肌是显著地有效的，弛缓的效果取决于 verapamil 的集中。
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Effects of verapamil on cytosolic Ca2 + levels ([Ca2+]cyt) and contraction in fura-2-loaded rat aorta were examined. Norepinephrine (NE) induced a greater contraction than KC1 for a given increase in [Ca2+]cyt. Cumulative addition of verapamil decreased the NE-stimulatcd [Ca2+]cyt more strongly than contraction whereas verapamil decreased high K+-stimulated [Ca2+]cyt and contraction in parallel. In the presence of verapamil at a concentration needed to completely inhibit the high K+-induced increments, NE induced a transient increase, followed by a small sustained increase in [Ca2+]cyt which averaged 25% of that in the absence of verapamil. These changes were followed by a sustained contraction which averaged 60% of that in the absence of verapamil. In Ca2+-free solution, NE induced only a transient increase in (Ca2+]cyt whereas it induced a transient contraction, followed by a small sustained contraction. The second application of NE induced a small sustained contraction (10% of that in the presence of Ca2+) without increasing [Ca2 +]cyt. These changes were not affected by verapamil. These results suggest that verapamil inhibits NE-induced increase in [Ca2+]cyt, but not the Ca2+-sensitization or Ca2 +-independent contraction, and this may be the reason why the NE-induced contraction is less sensitive to verapamil than that induced by high K+.
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当教室で樹立した人培養腎癌細胞株 (NUR) および人正常腎細胞 (PHK) を用い, ビンクリスチン (VCR), アドリアマイシン (ADM), シスプラチン (CDDP) に対する verapamil の効果増強作用について検討した. 殺細胞効果については, 細胞の増殖曲線, 3H-thymidine incorporation 法で検討した. また細胞内における3H-VCR, 3H-daunomycin の取り込みを経時的に測定し, 取り込みおよび放出に対する verapamil の影響をみた. verapamil の濃度は細胞毒性を示さない1.0μg/mlとした. verapamil は NURcell の増殖曲線, 3H-thymidine incorporation のいずれにおいてもADM, VCR, CDDPの殺細胞効果を増強させ, 3H-thymidine incorporation の抑制でみるとIC50 (drug concentration for 50% inhibition) は各々制癌剤単独で0.095, 4.81, 1.01μg/mlであったものが, verapamil 1.0μg/mlの併用で, 0.039, 1.29, 0.508μg/mlとなった. またNUR cell に対し, ADMの効果増強を生じる verapamil の最小濃度は, 約0.1μg/mlであり, その増強効果は濃度依存性に高められた. 3H-VCR, 3H-daunomycin のNUR cell への取り込みは verapamil によって, いずれも増加した. しかし細胞外放出に対しては, 3H-VCRは verapamil によって抑制される傾向を示したが, 3H-daunomycin については, その影響を認めなかった. PHK cell についても 3H-thymidine incorporation によってVCR, ADM, CDDPに対する verapamil の影響を検討したが, いずれも軽度であった. また, PHK cell への3H-VCR, 3H-daunomycin の取り込みに対する verapamil の影響も極軽度であった.
Thymidine
IC50
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Effects of ouabain (10-12M to 10-5M) on the simultaneously recorded transmembrane action potential and contraction; and (Na+-K+)-activated membrane ATPase of human papillary muscles were investigated. Ouabain in the concentration of 10-12M did not affect the transmembrane potential, contraction and (Na+-K+)-ATPase activity. Ouabain in the concentrations of 10-11 to 10-7M produced a concentration dependent inhibition of (Na+-K+)-APTase associated with shortening of action potential duration and increase in contraction. Ouabain (10-7M) produced a time dependent inhibition of the (Na+-K+)-ATPase associated with the shortening of action potential duration and increase in contraction. Ouabain in the concentration of 10-5M produced an initial marked increase in contraction which was shortly followed by a decrease in contraction and an increase in tone. The muscles developed contracture within 15 to 20min. This concentration of ouabain inhibited the (Na+-K+)-ATPase completely. These results suggest that there is a relation between the inhibition of the (Na+-K+)-ATPase and shortening of action potential duration associated with an increase in contraction. Human papillary muscles seem to be very sensitive to the effect of ouabain.
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We studied the relationship between the atrioventricular nodal functional refractory period (FRP) and refractoriness by mathematical analysis and by measurement during antegrade Wenckebach cycles in 16 dogs. The FRP relates directly to the conduction time of the control beat, and inversely to the coordinates of the point on the A'-H' vs. A-A refractory curve where the slope is -1. The FRP can vary without any change in refractoriness as measured by the effective refractory period (ERP) or the refractory curve. In 16 dogs the ERP and the FRP were measured during 4:3 Wenckebach cycles. Because of changes in the control conduction times, the FRP declined and did not reflect the progressive increase in refractoriness recorded during Wenckebach cycles. The FRP is a complex parameter and does not reliably measure refractoriness.
Refractory (planetary science)
Effective refractory period
Beat (acoustics)
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The aim of this work was to determine the influence of ethanol on the antiarrhythmic activity of verapamil in the model of calcium arrhythmia in rats non-dependent and dependent on ethanol. The results of the experiment show that a combined, single administration of ethanol and verapamil attenuates in a statistically significant manner the antiarrhythmic effect of verapamil. Ethanol administered repeatedly together with verapamil does not diminish the antiarrhythmic activity of verapamil.
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Effects of verapamil on cytosolic Ca2+ levels ([Ca2+]cyt) and contraction in fura-2-loaded rat aorta were examined. Norepinephrine (NE) induced a greater contraction than KCl for a given increase in [Ca2+]cyt. Cumulative addition of verapamil decreased the NE-stimulated [Ca2+]cyt more strongly than contraction whereas verapamil decreased high K(+)-stimulated [Ca2+]cyt and contraction in parallel. In the presence of verapamil at a concentration needed to completely inhibit the high K(+)-induced increments, NE induced a transient increase, followed by a small sustained increase in [Ca2+]cyt which averaged 25% of that in the absence of verapamil. These changes were followed by a sustained contraction which averaged 60% of that in the absence of verapamil. In Ca2(+)-free solution, NE induced only a transient increase in [Ca2+]cyt whereas it induced a transient contraction, followed by a small sustained contraction. The second application of NE induced a small sustained contraction (10% of that in the presence of Ca2+) without increasing [Ca2+]cyt. These changes were not affected by verapamil. These results suggest that verapamil inhibits NE-induced increase in [Ca2+]cyt, but not the Ca2(+)-sensitization or Ca2(+)-independent contraction, and this may be the reason why the NE-induced contraction is less sensitive to verapamil than that induced by high K+.
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