scholarly journals Effects of thapsigargin and cyclopiazonic acid on twitch force and sarcoplasmic reticulum Ca2+ content of rabbit ventricular muscle.

1993 ◽  
Vol 73 (5) ◽  
pp. 813-819 ◽  
Author(s):  
S Baudet ◽  
R Shaoulian ◽  
D M Bers
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cyclopiazonic Acid ◽  
Ventricular Muscle ◽  
Twitch Force ◽  
Rabbit Ventricular Muscle

The mechanism of ryanodine action in rabbit ventricular muscle evaluated with Ca-selective microelectrodes and rapid cooling contractures

1987 ◽  
Vol 65 (4) ◽  
pp. 610-618 ◽  
Author(s):  
Donald M. Bers ◽  
John H. B. Bridge ◽  
Kenneth T. MacLeod
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Extracellular Space ◽  
Repetitive Stimulation ◽  
Ventricular Muscle ◽  
Half Time ◽  
Rapid Cooling ◽  
Ca Uptake ◽  
Rabbit Ventricular Muscle ◽  
Independent Assay ◽  
Cellular Ca

Cellular Ca uptake and efflux in rabbit ventricular muscle was measured using double-barreled Ca microelectrodes in the extracellular space. When repetitive stimulation was stopped there was a slow loss of cellular Ca. Upon resumption of stimulation Ca was taken up by the cells. These Ca movements are thought to represent the loss of Ca from the sarcoplasmic reticulum and the cell during rest and the refilling of the sarcoplasmic reticulum during stimulation. Ryanodine (100 nM) greatly enhanced both the efflux of Ca during rest and the uptake of Ca induced by stimulation. These results are consistent with the conclusions drawn below, but they are dependent upon the interpretation that these extracellular Ca depletions are indicative of sarcoplasmic reticulum Ca movements. To examine further this process, contractures induced by rapid cooling to 0 °C were used as an independent assay of sarcoplasmic reticulum Ca content. These rapid cooling contractures were smaller after longer rest intervals (declining with a half time of 1.5 min). In the presence of ryanodine, the rapid cooling contracture immediately after a contraction was greater than that seen under control conditions. However, in the presence of ryanodine these rapid cooling contractures decline as a function of rest duration with a half time of about 1 s. These results suggest that in the presence of ryanodine the sarcoplasmic reticulum can still take up Ca, but that it also loses this Ca very rapidly at the onset of rest. Caffeine (20 mM) inhibits both the extracellular Ca depletions and the rapid cooling contractures that are attributed to the sarcoplasmic reticulum Ca content changes (in the presence or absence of ryanodine). These results suggest the following two actions of ryanodine: (i) inhibition of sarcoplasmic reticulum Ca release into the cytoplasm upon activation, and (ii) enhancement of Ca loss from the sarcoplasmic reticulum upon the termination of stimulation and extrusion from the cell without activation of appreciable tension.

scholarly journals Relationships between the sarcoplasmic reticulum and sarcolemmal calcium transport revealed by rapidly cooling rabbit ventricular muscle.

1986 ◽  
Vol 88 (4) ◽  
pp. 437-473 ◽  
Author(s):  
J H Bridge
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Transport ◽  
Fourier Spectrum ◽  
Papillary Muscles ◽  
Ventricular Muscle ◽  
Relative Index ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Muscle Cooling ◽  
Rabbit Ventricular Muscle

Rabbit right ventricular papillary muscles were cooled from 30 to approximately 1 degree C immediately after discontinuing electrical stimulation (0.5 Hz). This produced a contracture that was 30-50% of the preceding twitch magnitude and required 20-30 s to develop. The contractures were identical in cooling solutions with normal (144 mM) or low (2.0 mM) Na. They were therefore not Na-withdrawal contractures. Contracture activation was considerably slower than muscle cooling (approximately 2.5 s to cool below 2 degrees C). Cooling contractures were suppressed by caffeine treatment (10.0 mM). Rapid cooling did not cause sufficient membrane depolarization (16.5 +/- 1.2 mV after 30 s of cooling) to produce either a voltage-dependent activation of contracture or a gated entry of Ca from the extracellular space. Contractures induced by treating resting muscles with 5 X 10(-5) M strophanthidin at 30 degrees C exhibited pronounced tension noise. The Fourier spectrum of this noise revealed a periodic component (2-3 Hz) that disappeared when the muscle was cooled. Cooling contractures decayed with rest (t1/2 = 71.0 +/- 9.3 s). This decay accelerated in the presence of 10.0 mM caffeine and was prevented and to some extent reversed when extracellular Na was reduced to 2.0 mM. 20 min of rest resulted in a net decline in intracellular Ca content of 1.29 +/- 0.38 mmol/kg dry wt. I infer that cooling contractures are principally activated by Ca from the sarcoplasmic reticulum (SR). The properties of these contractures suggest that they may provide a convenient relative index of the availability of SR Ca for contraction. The rest decay of cooling contractures (and hence the decay in the availability of activating Ca) is consistent with the measured loss in analytic Ca during rest. The results suggest that contraction in heart muscle can be regulated by an interaction between sarcolemmal and SR Ca transport.

Ryanodine and the calcium content of cardiac SR assessed by caffeine and rapid cooling contractures

1987 ◽  
Vol 253 (3) ◽  
pp. C408-C415 ◽  
Author(s):  
D. M. Bers
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Content ◽  
Ventricular Muscle ◽  
Free Medium ◽  
Rapid Cooling ◽  
Relative Index ◽  
Tension Level ◽  
Resting Tension ◽  
Rabbit Ventricular Muscle ◽  
Caffeine Contractures

The ability of rabbit ventricular muscle sarcoplasmic reticulum (SR) to accumulate and retain Ca during Na-free perfusion was assessed using caffeine contractures and rapid cooling contractures (RCC). Muscles were exposed to a Na-free medium for 15 min, during which time a transient contracture developed and relaxed back to the resting tension level. Muscles were then either exposed to 20 mM caffeine or rapidly cooled to less than 5 degrees C, both of which produced large contractures. The magnitudes of those contractures are believed to be a relative index of SR Ca content. Reduction of extracellular [Ca] from 2 to 0.2 mM did not significantly alter the magnitude of either Na-free caffeine contractures or RCC. These are not the maximum contractures that can be obtained. The possibility that low extracellular [Ca] ([Ca]o) may increase passive Ca permeability is suggested in explanation of this effect. After equilibration with 100 nM ryanodine, both Na-free caffeine contractures and RCC are virtually eliminated. This suggests that even if the SR could accumulate Ca during the initial Na-free exposure in the presence of ryanodine, it could not retain that Ca in Na-free medium. It is proposed that the sarcolemmal Ca pump can extrude Ca from the cells at a rate sufficient to deplete the ryanodine-treated SR. When removal of Na was accompanied by increase of [K]o (to 12, 20, or 30 mM), the Na-free RCC were enhanced. Increasing [K]o during Na-free superfusion in the presence of ryanodine resulted in demonstrable RCC that were graded with [K] and completely suppressed by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of rest duration and ryanodine on changes of extracellular [Ca] in cardiac muscle from rabbits

1987 ◽  
Vol 253 (3) ◽  
pp. C398-C407 ◽  
Author(s):  
K. T. MacLeod ◽  
D. M. Bers
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Extracellular Space ◽  
Ventricular Muscle ◽  
Rest Interval ◽  
Continuous Stimulation ◽  
Rabbit Ventricular Muscle ◽  
Interpretive Framework ◽  
Rest Intervals

Cumulative depletions of extracellular Ca were measured using double-barreled Ca-sensitive microelectrodes in the extracellular space of rabbit ventricular muscle. Depletions were produced by 1-Hz stimulation after rest intervals of 10 s to 10 min. With longer rest intervals, depletion size increased while the first postrest contraction decreased in a reciprocal manner. The depletions may represent refilling of sarcoplasmic reticulum (SR) Ca stores that have become partially depleted of Ca during the rest. Within this interpretive framework, the longer the rest interval the lower the SR Ca content, so the SR is then capable of taking up larger amounts of Ca. This may be related to the rest decay of tension of the first postrest beat, since this is thought to be SR dependent. Ryanodine (1 microM) increased the size of the depletions after short rest intervals (less than 2 min) but not after longer (greater than or equal to 2 min) intervals. Ryanodine also increased the rate of Ca loss from the cell on cessation of stimulation. This increased rate of Ca loss with ryanodine may deplete the SR of Ca such that more Ca can be taken up during subsequent stimulation than in untreated muscles. Thus cumulative depletions after short rest intervals are enhanced by ryanodine. When a Ca load was produced during 1) quiescence [by removal of extracellular Na (Nao)] or 2) continuous stimulation (in the presence of 3 microM acetylstrophanthidin), addition of ryanodine (5-10 microM) did not produce any apparent Ca loss. Caffeine (10 mM), added after ryanodine, induced contractures accompanied by Ca efflux, implying there was Ca in the SR after ryanodine exposure. The results of other investigators have suggested that ryanodine may inhibit cardiac SR Ca release. The present study suggests that ryanodine also enhances the loss of cellular (and probably SR) Ca on cessation of stimulation but not when applied during continuous stimulation or quiescence.

Na+ entry via store-operated channels modulates Ca2+signaling in arterial myocytes

2000 ◽  
Vol 278 (1) ◽  
pp. C163-C173 ◽  
Author(s):  
Assaf Arnon ◽  
John M. Hamlyn ◽  
Mordecai P. Blaustein
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cyclopiazonic Acid ◽  
General Mechanism ◽  
Tetraacetic Acid ◽  
Pump Activity ◽  
In Cells

In many nonexcitable cells, hormones and neurotransmitters activate Na+ influx and mobilize Ca2+ from intracellular stores. The stores are replenished by Ca2+influx via “store-operated” Ca2+ channels (SOC). The main routes of Na+ entry in these cells are unresolved, and no role for Na+ in signaling has been recognized. We demonstrate that the SOC are a major Na+ entry route in arterial myocytes. Unloading of the Ca2+stores with cyclopiazonic acid (a sarcoplasmic reticulum Ca2+ pump inhibitor) and caffeine induces a large external Na+-dependent rise in the cytosolic Na+ concentration. One component of this rise in cytosolic Na+ concentration is likely due to Na+/Ca2+exchange; it depends on elevation of cytosolic Ca2+ and is insensitive to 10 mM Mg2+ and 10 μM La3+. Another component is inhibited by Mg2+ and La3+, blockers of SOC; this component persists in cells preloaded with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid to buffer Ca2+ transients and prevent Na+/Ca2+exchange-mediated Na+ entry. This Na+ entry apparently is mediated by SOC. The Na+ entry influences Na+ pump activity and Na+/Ca2+exchange and has unexpectedly large effects on cell-wide Ca2+ signaling. The SOC pathway may be a general mechanism by which Na+ participates in signaling in many types of cells.

scholarly journals Energy expenditure by Ba2+contracture in rat ventricular slices derives from cross-bridge cycling

1999 ◽  
Vol 277 (1) ◽  
pp. H74-H79 ◽  
Author(s):  
Hisaharu Kohzuki ◽  
Hiromi Misawa ◽  
Susumu Sakata ◽  
Yoshimi Ohga ◽  
Hiroyuki Suga ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Energy Expenditure ◽  
Cyclopiazonic Acid ◽  
Left Ventricular ◽  
Basal Metabolism ◽  
Dependent Manner ◽  
Tyrode Solution ◽  
Cross Bridge ◽  
Butanedione Monoxime ◽  
Dose Dependent

To clarify the energy-expenditure mechanism during Ba2+ contracture of mechanically unloaded rat left ventricular (LV) slices, we measured myocardial O2 consumption (V˙o 2) of quiescent slices in Ca2+-free Tyrode solution andV˙o 2 during Ba2+ contracture by substituting Ca2+ with Ba2+. We then investigated the effects of cyclopiazonic acid (CPA) and 2,3-butanedione monoxime (BDM) on the Ba2+ contractureV˙o 2. The Ca2+-freeV˙o 2 corresponds to that of basal metabolism (2.32 ± 0.53 ml O2 ⋅ min−1 ⋅ 100 g LV−1). Ba2+ increased theV˙o 2 in a dose-dependent manner (from 0.3 to 3.0 mmol/l) from 110 to 150% of basal metabolic V˙o 2. Blockade of the sarcoplasmic reticulum (SR) Ca2+ pump by CPA (10 μmol/l) did not at all decrease the Ba2+-activatedV˙o 2. BDM (5 mmol/l), which specifically inhibits cross-bridge cycling, reduced the Ba2+activatedV˙o 2 almost to basal metabolic V˙o 2. These energetic results revealed that the Ba2+-activatedV˙o 2 was used for the cross-bridge cycling but not for the Ca2+ handling by the SR Ca2+ pump.

Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine

2004 ◽  
Vol 286 (3) ◽  
pp. L531-L538 ◽  
Author(s):  
Zhigang Hong ◽  
Andrea Olschewski ◽  
Helen L. Reeve ◽  
Daniel P. Nelson ◽  
Fangxiao Hong ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Pulmonary Arteries ◽  
Cyclopiazonic Acid ◽  
Cytosolic Calcium ◽  
Ring Contraction ◽  
Pulmonary Vasoconstriction ◽  
Reduced Ring ◽  
Dose Dependent Decrease ◽  
Trisphosphate Receptor ◽  
Dose Dependent

The anorectic agent dexfenfluramine (dex) causes the development of primary pulmonary hypertension in susceptible patients by an unknown mechanism. We compared the effects of dex with those of its major metabolite, nordexfenfluamine (nordex), in the isolated perfused rat lung and in isolated rings of resistance pulmonary arteries. Nordex caused a dose-dependent and more intense vasoconstriction, which can be inhibited by the nonspecific 5-hydroxytryptamine type 2 (5-HT2) blocker ketanserin. Similarly a rise in cytosolic calcium concentration ([Ca2+]i) in dispersed pulmonary artery smooth muscle cells (PASMCs) induced by nordex could be prevented by ketanserin. Unlike prior observations with dex, nordex did not inhibit K+ current or cause depolarization in PASMCs. Removal of Ca2+ from the tissue bath or addition of nifedipine (1 μM) reduced ring contraction to nordex by 60 ± 9 and 63 ± 4%, respectively. The addition of 2-aminoethoxydiphenyl borate (2-APB), a blocker of store-operated channels and the inositol 1,4,5-trisphosphate receptor, caused a dose-dependent decrease in the ring contraction elicited by nordex. The combination of 2-APB (10 μM) and nifedipine (1 μM) completely ablated the nordex contraction. Likewise the release of Ca2+ from the sarcoplasmic reticulum by cyclopiazonic acid markedly reduced the nordex contraction while leaving the KCl contraction unchanged. We conclude that nordex may be responsible for much of the vasoconstriction stimulated by dex, through the activation of 5-HT2 receptors and that the [Ca2+]i increase in rat PASMCs caused by dex/nordex is due to both influx of extracellular Ca2+ and release of Ca2+ from the sarcoplasmic reticulum.

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