A Comparative Study of Effects of Isoproterenol and Dihydroouabain on Calcium transients and Contraction in Cultured Rat Ventricular Cells

Tatsukawa, Youichi; Arita, Makoto; Kiyosue, Tatsuto; Mikuriya, Yoshiaki; Nasu, Masaru

doi:10.1006/jmcc.1993.1083

Cited by 23 publications

(11 citation statements)

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“…Ryanodine (10 }~M) per se slightly decreased sCa, markedly increased dCa, and prolonged the time to peak and the half-life of the Ca 2÷ transient, as reported previously [12]. Increases in dCa were dependent on the frequency of stimulation that is, the higher the stimulation frequency, the greater the increase in dCa (see Fig.…”

Section: Effects Of Ryanodine On Ca Z+ Transientssupporting

confidence: 57%

“…Gallopamil decreased the dCa as well, but only at relatively high rates of stimulation (1.0 Hz). A similar decrease in dCa was noted when the external Ca ~÷ concentrations was decreased in this preparation, which was attributed to a decrease in the calcium inward current [12]. However, it has been reported that low concentrations of gallopamil (10-300 riM) decreased Ca 2÷ efflux through Ca 2÷ channels of the sarcoplasmic reticulum (SR) prepared from bovine ventricular muscles, although much higher concentrations, as used in our experiment (1 ~M), were ineffective [20].…”

Section: Effects Of Gallopamil On Ca 2+ Transientsmentioning

confidence: 56%

“…Primary cultured cardiomyocytes were prepared from ventricles of 1-to 5-day-old neonatal Wistar rats of either sex, using the same methods as described in our previous study [12], which originated from Bollon et al [13]. This technique produced cell aggregates of 100-300 mm in diameter that were quiescent (5%) or beating synchronously (95%).…”

Section: Culture Of Ventricular Myocytesmentioning

confidence: 99%

“…The increase in dCa could be explained if the total removal rate of Ca 2÷ from the cytosol (per unit time) via the Ca2+-uptake mechanism of the SR, sarcolemmal Na÷-Ca 2÷ exchange, and the sarcolemmal Ca 2÷ pump was not sufficient to cope with the accumulation of intracellular Ca 2+ (per unit time) due to the ryanodine-induced Ca 2÷ leak (from the SR) and Ca 2÷ influx via the Ca ~÷ channels (which may increase as the rate of stimulation was increased). It is likely that the leakiness of the SR membrane to Ca 2÷ is responsible for the prolongation of the time to peak and the half-life of Ca 2+ transients, as discussed elsewhere [12].…”

Section: Effects Of Ryanodine On Ca Z+ Transientsmentioning

confidence: 99%

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Effects of KT-362, a sarcolemmal and intracellular calcium antagonist, on calcium transients of cultured neonatal rat ventricular cells: A comparison with gallopamil and ryanodine

Tatsukawa

Arita

1997

Cardiovasc Drug Ther

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We evaluated the effects of KT-362 (5-[3-([2-(3,4-dimethoxyphenyl)-ethyl]amino)-1-oxopropyl]-2,3,4,5, -tetrahydro-1,5-benzothiazepine fumarate), a putative intracellular calcium antagonist, on the intracellular free calcium concentration ([Ca2+]i) of cultured neonatal rat ventricular cells using microfluorometry of fura-2. The effects were compared with those of gallopamil (D-600), a sarcolemmal calcium channel antagonist, and ryanodine, a modulator of sarcoplasmic reticulum (SR) function. KT-362 decreased both systolic [Ca2+]i (sCa) and diastolic [Ca2+]i (dCa) in cell aggregates, in a concentration (1, 3, 10, and 30 microM) and stimulation frequency (0.2, 0.5, and 1.0 Hz) dependent manner. The time to peak of the Ca2+ transient was significantly prolonged by KT-362 at a concentration of 30 microM, while the half-life of the Ca2+ transient was prolonged at concentrations of > or = 10 microM. Gallopamil (1 microM) decreased both sCa and dCa in a frequency (0.2, 0.5, and 1.0 Hz) dependent fashion, as was the case for KT-362, but did not change the time course of Ca2+ transients. Ryanodine (10 microM) prolonged the time to peak and half-life of the Ca2+ transient, as was also the case for KT-362, while the effect of ryanodine on dCa differed from that of KT-362. Finally, the effect of KT-362 on Ca2+ transients could be mimicked by simultaneous application of gallopamil and ryanodine. These results suggest that KT-362 is a novel compound that exerts depressant effects on both sarcolemmal Ca2+ channels, and perhaps Ca2+ release channels of the sarcoplasmic reticulum, in cultured neonatal rat ventricular cells.

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Section: Effects Of Ryanodine On Ca Z+ Transientssupporting

confidence: 57%

Section: Effects Of Gallopamil On Ca 2+ Transientsmentioning

confidence: 56%

Section: Culture Of Ventricular Myocytesmentioning

confidence: 99%

Section: Effects Of Ryanodine On Ca Z+ Transientsmentioning

confidence: 99%

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Effects of KT-362, a sarcolemmal and intracellular calcium antagonist, on calcium transients of cultured neonatal rat ventricular cells: A comparison with gallopamil and ryanodine

Tatsukawa

Arita

1997

Cardiovasc Drug Ther

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“…KT-362 (100 FM) did not suppress the caffeine-induced transient increase in intracellular Ca2 + ([Ca' +Ii) and contractions of rat aortic strips immersed in Ca2+-free media (21). Interestingly, in the latter experiment, the addition of KT-362 ( 100 p M ) slightly increased [Ca2+Ii and tension, thereby suggesting that high concentrations of KT-362 release a small amount of Ca2+ from intracellular stores in rat aorta, as did ryanodine (at relatively low concentrations) in cultured rat ventricular cells (24). The effects of KT-362 on caffeine-sensitive component of Ca2+ stores have yet to be clarified.…”

mentioning

confidence: 89%

KT‐362, a Vasodilating and Antiarrhythmic Agent

Kiyosue

Ito

Cheng

et al. 1996

Cardiovascular Drug Reviews

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Key Words: Antiarrhythmic effect-KT-362-L-type Ca2+ channel-Myocardium-Na+ channel-Sarcoplasmic reticulum-Vascular smooth muscle. 3,4-dimethoxyphenyl]ethyl)amino] -1 -oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate} is a vasodilating and antiarrhythmic agent synthesized at the Kotobuki Pharmaceutical Co., Ltd. (Nagano, Japan). Its chemical structure resembles that of diltiazem (left half of the chemical structure shown in Fig. 1) and verapamil (the right half). KT-362 is a white powder (molecular weight 516) and is fairly soluble in water. PHARMACOLOGY Hemodynamic EffectsKT-362 decreases the heart rate in anesthetized laboratory animals (26) and increases the heart rate in conscious animals by autonomic reflex (7). Fig. 2 shows an example of the cardiovascular effects of in an anesthetized open-chest dog (26). Intravenously administered KT-362 (0.3-10 mg/kg, a bolus injection) decreased the left ventricular and mean arterial blood pressures and total peripheral resistance. As cardiac output increased, vasodilating and after-load reducing effects probably opposed the intrinsic negative inotropic effect of this drug on the myocardium. Similar results were obtained with verapamil at an effective dose more than 10 times lower than that of KT-362. Continuous infusion of KT-362 (150-300 kg/kg/min) decreased the heart rate, left ventricular pressure, and dP/dt , but these changes were not statistically significant (5 ,6918). Mechanism of Vasodilating ActionThe vasodilating action of KT-362 is attributed not only to inhibition of Ca2+ entry via voltage-gated Ca2+ channels, but also to inhibitory effects on Ca2+ release from nor-

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Mechanical stretch increases intracellular calcium concentration in cultured ventricular cells from neonatal rats

1997

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We investigated the effects of mechanical stretch on intracellular calcium concentration ([Ca2+]i) of cultured neonatal rat ventricular cells using microfluorometry with fura-2. Myocytes were cultured on laminin-coated silicon rubber and stretched by pulling the rubber with a manipulator. Myocytes were either mildly stretched (to less than 11.5% of control length), moderately so (to 115%-125% of control length), or extensively (to over 125% of the control length). "Quick stretches" (accomplished within 10s) of moderate to extensive intensities produced a large transient increase of [Ca2+]i in the early phase of stretch (30 s-2 min), followed by a small but sustained increase during the late phase of stretch (5-10 min). The initial transient increase in [Ca2+]i after the "quick stretch" was preserved in the presence of gallopamil (10(-7) M) or ryanodine (10(-5) M), but was absent in Ca(2+)-free medium or in the presence of gadolinium (10(-7) M). The late or steady state [Ca2+]i increase was observed in the presence of gadolinium, gallopamil, or ryanodine but was abolished in Ca(2+)-free medium. A steady-state increase in [Ca2+]i was also evoked by "slow stretch" in which cells were slowly pulled to the final length within 1-2 min. As the presence of external Ca2+ was indispensable, increased trans-sarcolemmal Ca2+ influx appears to be involved in both initial and steady-state increases in [Ca2+]i. The initial increase in [Ca2+]i after the "quick stretch" can be attributed to the activation of gadolinium-sensitive, stretch-activated channels.

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A Comparative Study of Effects of Isoproterenol and Dihydroouabain on Calcium transients and Contraction in Cultured Rat Ventricular Cells

Cited by 23 publications

References 0 publications

Effects of KT-362, a sarcolemmal and intracellular calcium antagonist, on calcium transients of cultured neonatal rat ventricular cells: A comparison with gallopamil and ryanodine

Effects of KT-362, a sarcolemmal and intracellular calcium antagonist, on calcium transients of cultured neonatal rat ventricular cells: A comparison with gallopamil and ryanodine

KT‐362, a Vasodilating and Antiarrhythmic Agent

Mechanical stretch increases intracellular calcium concentration in cultured ventricular cells from neonatal rats

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