Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats

Hattori, Yuya; Toyama, Junji; Kodama, Itsuo

doi:10.1093/cvr/25.8.622

Cited by 15 publications

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“…This concealed positive FFR is 21 of the animals in this study demonstrated this late phase. not associated with increased SR Ca release upon higher Thus, analogous to isolated papillary muscle, the results of rates of stimulation [26], but is correlated with increased 21 this study are consistent with ryanodine induced transintracellular Ca levels. Thus, akin to MR, FFR amplifi- 21 21 formation of myocardial Ca handling from being precation is consistent with increased importance of SL Ca dominantly SR dependent to predominantly SL dependent.…”

Section: Essupporting

confidence: 76%

Ryanodine and the left ventricular force–interval and relaxation–interval relations in closed-chest dogs: insights on calcium handling

Prabhu

1998

Cardiovascular Research

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Objective: Although the myocardial force-interval and relaxation-interval relations are considered to be mechanical expressions of 21 21 myocardial Ca handling, correlation of these phenomena with altered Ca kinetics in the intact state is limited. Thus, I sought to 21 determine the impact of selective impairment of physiologic sarcoplasmic reticulum Ca release, achieved by the use of the drug ryanodine, on these relations in the intact animal. Methods: Twelve dogs instrumented with left ventricular manometers and piezoelectric dimension crystals were studied before and after ryanodine (4 mg / kg intravenously). End-systolic elastance was measured at paced heart rates of 120-180 bpm to determine the force-frequency response. Mechanical restitution and relaxation restitution were determined by measuring contractile (single beat elastance) and relaxation (peak negative dP/dt) responses for beats delivered at graded extrasystolic intervals, with normalized responses expressed as a function of extrasystolic interval.

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Section: Essupporting

confidence: 76%

Ryanodine and the left ventricular force–interval and relaxation–interval relations in closed-chest dogs: insights on calcium handling

Prabhu

1998

Cardiovascular Research

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“…The authors suggested that this increase in diastolic Ca 2ϩ contributed to positive inotropic effects by increasing SR stores (19). Interestingly, Hattori et al (20) showed that increases in diastolic Ca 2ϩ might play a direct role in mediating positive staircases, which were generated by stimulating cardiac myocytes following a period of rest. In this study, positive staircases were directly related to progressive increases in diastolic [Ca 2ϩ ] and were preserved when SR Ca 2ϩ release was blocked by ryanodine (20).…”

mentioning

confidence: 99%

“…Interestingly, Hattori et al (20) showed that increases in diastolic Ca 2ϩ might play a direct role in mediating positive staircases, which were generated by stimulating cardiac myocytes following a period of rest. In this study, positive staircases were directly related to progressive increases in diastolic [Ca 2ϩ ] and were preserved when SR Ca 2ϩ release was blocked by ryanodine (20). Ryanodine should remove the contribution of SR Ca 2ϩ release to staircases, and therefore this observation suggests a role for changes in diastolic Ca 2ϩ in generation of staircases (20).…”

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confidence: 99%

Increases in diastolic [Ca²⁺] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca²⁺ transients

Shutt

Ferrier²,

Howlett³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Increases in contraction amplitude following rest or in elevated extracellular Ca(2+) concentration ([Ca(2+)]) have been attributed to increased sarcoplasmic reticulum (SR) Ca(2+) stores and/or increased trigger Ca(2+). However, either manipulation also may elevate diastolic [Ca(2+)]. The objective of this study was to determine whether elevation of diastolic [Ca(2+)] could contribute to positive inotropy in isolated ventricular myocytes. Voltage-clamp experiments were conducted with high-resistance microelectrodes in isolated myocytes at 37 degrees C. Intracellular free [Ca(2+)] was measured with fura-2, and cell shortening was measured with an edge detector. SR Ca(2+) stores were assessed with 10 mM caffeine (0 mM Na(+), 0 mM Ca(2+)). Following a period of rest, cells were activated with trains of pulses, which generated contractions of increasing amplitude, called positive staircases. Positive staircases were accompanied by increasing diastolic [Ca(2+)] but no change in Ca(2+) transient amplitudes. When extracellular [Ca(2+)] was elevated from 2.0 to 5.0 mM, resting intracellular [Ca(2+)] increased and resting cell length decreased. Amplitudes of contractions and L-type Ca(2+) current increased in elevated extracellular [Ca(2+)], although SR Ca(2+) stores, assessed by rapid application of caffeine, did not increase. Although Ca(2+) transient amplitude did not increase in 5.0 mM extracellular [Ca(2+)], diastolic [Ca(2+)] continued to increase with increasing extracellular [Ca(2+)]. These data suggest that increased diastolic [Ca(2+)] contributes to positive inotropy following rest or with increasing extracellular [Ca(2+)] in guinea pig ventricular myocytes.

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“…This suggests that an increase of intracellular calcium level is associated with ricin's toxicity. Based on studies of single myocardial cells, a cumulative increase in resting ICa2+], can result from Ca2+ handling by the sarcoplasmic reticulum (21). The mechanism for this rise in [Ca2+], can be secondary to decreased calcium uptake by the sarcoplasmic reticula (22) or through increased Na+-Ca2+ exchange (23).…”

Section: Discussionmentioning

confidence: 99%

Ricin disturbs calcium homeostasis in the rabbit heart

Hsu

Fugate

et al. 1995

J. Biochem. Toxicol.

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Ricin, a toxic lectin from the castor bean, affects the cardiovascular system. Because calcium is very important in cardiotoxicity and cell intoxication, we studied the effects of ricin pretreatment to rabbits on basal intracellular calcium levels and calcium uptake and release from isolated papillary muscle, microsomes, and mitochondria. An increase in basal intracellular calcium levels was observed. Ricin pretreatment nearly doubled the intracellular-free Ca2+ concentration as measured by fura-2 fluorescence microscopy in isolated myocytes (p = 0.002). Ricin did not alter basal calcium efflux in isolated papillary muscles. However, ricin inhibited the NE-induced calcium efflux (expressed as fractional efflux ratios) in papillary muscles from rabbits receiving the minimum lethal dose of ricin at 25-35 minutes (p = 0.002 and 0.003, respectively). Ricin depressed basal calcium uptake into isolated papillary muscles at 5 minutes (mean +/- SEM, mumol/g wet weight) (control: 3.68 +/- 0.57; ricin: 2.31 +/- 0.28, p = 0.045, n = 6). Ricin pretreatment significantly depressed calcium uptake into microsomes (mean +/- SEM, mumol/g protein) (control: 9.9 +/- 1.9; ricin: 3.1 +/- 1.9, p = 0.025, n = 6). Calcium uptake into mitochondria was increased at the beginning (2 minutes, p = 0.048), but not thereafter. Thus, administration of ricin disturbed calcium homeostasis in the rabbit heart, which may be at least partially responsible for altering cardiac function and myocardial cell death.

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Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats

Cited by 15 publications

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Ryanodine and the left ventricular force–interval and relaxation–interval relations in closed-chest dogs: insights on calcium handling

Ryanodine and the left ventricular force–interval and relaxation–interval relations in closed-chest dogs: insights on calcium handling

Increases in diastolic [Ca²⁺] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca²⁺ transients

Ricin disturbs calcium homeostasis in the rabbit heart

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Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats

Cited by 15 publications

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Ryanodine and the left ventricular force–interval and relaxation–interval relations in closed-chest dogs: insights on calcium handling

Ryanodine and the left ventricular force–interval and relaxation–interval relations in closed-chest dogs: insights on calcium handling

Increases in diastolic [Ca2+] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca2+ transients

Ricin disturbs calcium homeostasis in the rabbit heart

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Increases in diastolic [Ca²⁺] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca²⁺ transients