scholarly journals Unbalance Between Sarcoplasmic Reticulum Ca2 + Uptake and Release: A First Step Toward Ca2 + Triggered Arrhythmias and Cardiac Damage

2020 ◽  
Vol 10 ◽  
Author(s):  
Marilén Federico ◽  
Carlos A. Valverde ◽  
Alicia Mattiazzi ◽  
Julieta Palomeque
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Damage ◽  
Triggered Arrhythmias ◽  
Uptake And Release

scholarly journals A model for the uptake and release of Ca2+ by sarcoplasmic reticulum

1987 ◽  
Vol 245 (3) ◽  
pp. 739-749 ◽  
Author(s):  
G W Gould ◽  
J M McWhirter ◽  
J M East ◽  
A G Lee
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Atpase Activity ◽  
External Medium ◽  
Spontaneous Release ◽  
Calculated Concentration ◽  
Effects Of Ph ◽  
Hydrolysis Of ◽  
Uptake And Release

On addition of ATP to vesicles derived from the sarcoplasmic reticulum (SR) of skeletal muscle, Ca2+ is accumulated from the external medium. Following uptake, spontaneous release of Ca2+ occurs in the presence or in the absence of ATP. These processes of Ca2+ uptake and release were simulated by using the models derived for ATPase activity [Gould, East, Froud, McWhirter, Stefanova & Lee (1986) Biochem. J. 237, 217-227; Stefanova, Napier, East & Lee (1987) Biochem. J. 245, 723-730] and for Ca2+ release from passively loaded vesicles [McWhirter, Gould, East & Lee (1987) Biochem. J. 245, 713-722]. The simulations are consistent with measurements of the effects of pH, K+, Ca2+ and Mg2+ on uptake and release of Ca2+. The increase in maximal Ca2+ accumulation observed in the presence of maleate is explained in terms of complexing of Ca2+ and maleate within the SR. The calculated concentration of ADP generated by hydrolysis of ATP has a large effect on the simulations. The effects of an ATP-regenerating system on the measured Ca2+ uptake is explained in terms of both removal of ADP and precipitation of Ca3(PO4)2 within the vesicles. It is concluded that both the process of Ca2+ uptake and the process of Ca2+ release seen with SR vesicles can be interpreted quantitatively in terms solely of the properties of the Ca2+ + Mg2+-activated ATPase.

Free radicals enhance Na+/Ca2+ exchange in ventricular myocytes

1996 ◽  
Vol 271 (3) ◽  
pp. H823-H833 ◽  
Author(s):  
J. I. Goldhaber
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Similar Response ◽  
Inward Current ◽  
Oxygen Derived Free Radicals ◽  
Triggered Arrhythmias ◽  
Rabbit Ventricular Myocytes ◽  
Generating System

Oxygen-derived free radicals (OFR) have been implicated in the pathogenesis of intracellular Ca2+ overload and the arrhythmias that characterize cardiac reperfusion. These arrhythmias may in large part be due to activation of the pathological transient inward current (ITI). However, the identity of the ITI generated by OFR is uncertain. We previously found that H2O2, an OFR-generating compound, markedly stimulated the ITI elicited by brief caffeine pulses in patch-clamped guinea pig ventricular myocytes. In the present study, using patch-clamped rabbit ventricular myocytes loaded with the Ca(2+)-sensitive indicator fura 2, we have further characterized this ITI and have identified its major component to be Na+/Ca2+ exchange based on its dependence on extracellular Na+ and sarcoplasmic reticulum Ca2+ release, its sensitivity to Ni2+, and the effects of its inhibition on relaxation. The effect on ITI was not unique to H2O2, because another free radical-generating system, xanthine + xanthine oxidase, produced a similar response. We hypothesize that enhancement of Na+/Ca2+ exchange by OFR during reperfusion, when intracellular Na+ is elevated, may promote intracellular Ca2+ overload and triggered arrhythmias.

scholarly journals Phospholamban Knockout Breaks Arrhythmogenic Ca 2+ Waves and Suppresses Catecholaminergic Polymorphic Ventricular Tachycardia in Mice

2013 ◽  
Vol 113 (5) ◽  
pp. 517-526 ◽  
Author(s):  
Yunlong Bai ◽  
Peter P. Jones ◽  
Jiqing Guo ◽  
Xiaowei Zhong ◽  
Robert B. Clark ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Mouse Model ◽  
Ventricular Myocytes ◽  
Mutant Mice ◽  
Polymorphic Ventricular Tachycardia ◽  
Patch Clamp Recording ◽  
Plasmic Reticulum ◽  
Paradoxical Effects ◽  
Triggered Arrhythmias ◽  
The Impact

Rationale : Phospholamban (PLN) is an inhibitor of cardiac sarco(endo)plasmic reticulum Ca 2+ ATPase. PLN knockout (PLN-KO) enhances sarcoplasmic reticulum Ca 2+ load and Ca 2+ leak. Conversely, PLN-KO accelerates Ca 2+ sequestration and aborts arrhythmogenic spontaneous Ca 2+ waves (SCWs). An important question is whether these seemingly paradoxical effects of PLN-KO exacerbate or protect against Ca 2+ -triggered arrhythmias. Objective : We investigate the impact of PLN-KO on SCWs, triggered activities, and stress-induced ventricular tachyarrhythmias (VTs) in a mouse model of cardiac ryanodine-receptor (RyR2)-linked catecholaminergic polymorphic VT. Methods and Results : We generated a PLN-deficient, RyR2-mutant mouse model (PLN −/− /RyR2-R4496C +/− ) by crossbreeding PLN-KO mice with catecholaminergic polymorphic VT–associated RyR2-R4496C mutant mice. Ca 2+ imaging and patch-clamp recording revealed cell-wide propagating SCWs and triggered activities in RyR2-R4496C +/− ventricular myocytes during sarcoplasmic reticulum Ca 2+ overload. PLN-KO fragmented these cell-wide SCWs into mini-waves and Ca 2+ sparks and suppressed the triggered activities evoked by sarcoplasmic reticulum Ca 2+ overload. Importantly, these effects of PLN-KO were reverted by partially inhibiting sarco(endo)plasmic reticulum Ca 2+ ATPase with 2,5-di-tert-butylhydroquinone. However, Bay K, caffeine, or Li + failed to convert mini-waves to cell-wide SCWs in PLN −/− /RyR2-R4496C +/− ventricular myocytes. Furthermore, ECG analysis showed that PLN-KO mice are not susceptible to stress-induced VTs. On the contrary, PLN-KO protected RyR2-R4496C mutant mice from stress-induced VTs. Conclusions : Our results demonstrate that despite severe sarcoplasmic reticulum Ca 2+ leak, PLN-KO suppresses triggered activities and stress-induced VTs in a mouse model of catecholaminergic polymorphic VT. These data suggest that breaking up cell-wide propagating SCWs by enhancing Ca 2+ sequestration represents an effective approach for suppressing Ca 2+ -triggered arrhythmias.

Intracellular Cl− fluxes play a novel role in Ca2+ handling in airway smooth muscle

2006 ◽  
Vol 290 (6) ◽  
pp. L1146-L1153 ◽  
Author(s):  
Simon Hirota ◽  
Nancy Trimble ◽  
Evi Pertens ◽  
Luke J. Janssen
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Benzoic Acid ◽  
Airway Smooth Muscle ◽  
Channel Blocker ◽  
Negative Charge ◽  
Ryanodine Receptors ◽  
Inositol 1,4,5 Trisphosphate ◽  
Intracellular Ca ◽  
Uptake And Release

Intracellular Ca2+ is actively sequestered into the sarcoplasmic reticulum (SR), whereas the release of Ca2+ from the SR can be triggered by activation of the inositol 1,4,5-trisphosphate and ryanodine receptors. Uptake and release of Ca2+ across the SR membrane are electrogenic processes; accumulation of positive or negative charge across the SR membrane could electrostatically hinder the movement of Ca2+ into or out of the SR, respectively. We hypothesized that the movement of intracellular Cl− (Cl[Formula: see text]) across the SR membrane neutralizes the accumulation of charge that accompanies uptake and release of Ca2+. Thus inhibition of SR Cl− fluxes will reduce Ca2+ sequestration and agonist-induced release. The Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB; 10−4 M), previously shown to inhibit SR Cl− channels, significantly reduced the magnitude of successive acetylcholine-induced contractions of airway smooth muscle (ASM), suggesting a “run down” of sequestered Ca2+ within the SR. Niflumic acid (10−4 M), a structurally different Cl− channel blocker, had no such effect. Furthermore, NPPB significantly reduced caffeine-induced contraction and increases in intracellular Ca2+ concentration ([Ca2+]i). Depletion of Cl[Formula: see text], accomplished by bathing ASM strips in Cl−-free buffer, significantly reduced the magnitude of successive acetylcholine-induced contractions. In addition, Cl− depletion significantly reduced caffeine-induced increases in [Ca2+]i. Together these data suggest a novel role for Cl[Formula: see text] fluxes in Ca2+ handling in smooth muscle. Because the release of sequestered Ca2+ is the predominate source of Ca2+ for contraction of ASM, targeting Cl[Formula: see text] fluxes may prove useful in the control of ASM hyperresponsiveness associated with asthma.

Effect of acidosis on Ca2+uptake and release by sarcoplasmic reticulum of intact rat ventricular myocytes

1998 ◽  
Vol 275 (3) ◽  
pp. H977-H987 ◽  
Author(s):  
J. T. Hulme ◽  
C. H. Orchard
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Acid Solution ◽  
Ventricular Myocytes ◽  
Intracellular Acidosis ◽  
Patch Clamp Technique ◽  
Rat Ventricular Myocytes ◽  
Extracellular Acidosis ◽  
Intracellular Ca ◽  
Perforated Patch Clamp ◽  
Uptake And Release

The effect of acidosis on Ca2+ uptake and release by the sarcoplasmic reticulum (SR) of rat ventricular myocytes has been investigated. Intracellular Ca2+concentration ([Ca2+]i) was monitored using fura 2; the L-type Ca2+ current ( I Ca) was monitored using the perforated patch-clamp technique. Acidosis was produced either by superfusing the cells with an acid solution (intracellular and extracellular acidosis) or by NH4Cl withdrawal (intracellular acidosis). Both types of acidosis increased the amplitude, and slowed the declining phase, of the Ca2+transient. Application of caffeine produced a rise of [Ca2+]i, which declined in the continued presence of caffeine; the declining phase was slowed by the acid solution but was unaffected by NH4Cl withdrawal. Acidosis decreased the fraction of the caffeine-induced release that was released by electrical stimulation but had no effect on I Ca. It is concluded that acidosis inhibits SR Ca2+ uptake and Ca2+-induced Ca2+ release in intact myocytes but that these effects are compensated by an increase in SR Ca2+ content secondary to a rise in cytoplasmic [Ca2+].

Phospholamban mediates the beta-adrenergic-enhanced Ca2+ uptake in mammalian ventricular myocytes

1991 ◽  
Vol 261 (4) ◽  
pp. H1344-H1349 ◽  
Author(s):  
J. S. Sham ◽  
L. R. Jones ◽  
M. Morad
Keyword(s):  
Monoclonal Antibody ◽  
Sarcoplasmic Reticulum ◽  
Guinea Pig ◽  
Dissociation Constant ◽  
Molecular Mechanism ◽  
Heart Muscle ◽  
Ventricular Myocytes ◽  
Apparent Dissociation Constant ◽  
Relaxant Effect ◽  
Uptake And Release

To probe the molecular mechanism responsible for the relaxant effect of catecholamines in heart muscle, we studied the effect of a monoclonal antibody (2D12) against phospholamban in intact whole cell clamped guinea pig ventricular myocytes, in which intracellular Ca2+ transient and Ca2+ current were simultaneously measured. The antibody stimulated Ca2+ uptake in guinea pig ventricular sarcoplasmic reticular vesicles, shifting the apparent dissociation constant for activation by Ca2+ from 200 to 60 nM. The stimulatory effect of the antibody could be mimicked by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent kinase and could be blocked by phospholamban peptide 2-25. Dialysis of ventricular myocytes with the antibody enhanced the rate of uptake of Ca2+ and significantly suppressed the ability of isoproterenol to enhance the rate of uptake and release of Ca2+ by depolarizing pulses. These data suggest that not only is phosphorylation of phospholamban crucial in sequestration of Ca2+ by the sarcoplasmic reticulum, but that this process may account for the catecholamine-enhanced rate of Ca2+ uptake release in heart muscle.

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