Dual effects of cyclic ADP-ribose on sarcoplasmic reticulum Ca2+ release and storage in cardiac myocytes isolated from guinea-pig and rat ventricle☆

Macgregor, A; Rakovic, Stevan; Galione, Antony; Terrar, Derek A.

doi:10.1016/j.ceca.2006.10.005

Cited by 26 publications

(30 citation statements)

References 38 publications

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“…9 Cyclic ADP-ribose increases the amplitude of the Ca transient, 7 although it has been suggested that this may be a consequence of stimulation of the sarco-endoplasmic reticulum calcium ATPase (SERCA) rather than the RyR itself, 10 an explanation disputed by the original authors. 11 …”

Section: Introductionmentioning

confidence: 99%

Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions

Greensmith

Galli

Trafford

et al. 2014

Cardiovascular Research

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AimsMost of the calcium that activates contraction is released from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). It is controversial whether activators of the RyR produce a maintained increase in the amplitude of the systolic Ca transient. We therefore aimed to examine the effects of activation of the RyR in large animals under conditions designed to be as physiological as possible while simultaneously measuring SR and cytoplasmic Ca.Methods and resultsExperiments were performed on ventricular myocytes from canine and ovine hearts. Cytoplasmic Ca was measured with fluo-3 and SR Ca with mag-fura-2. Application of caffeine resulted in a brief increase in the amplitude of the systolic Ca transient accompanied by an increase of action potential duration. These effects disappeared with a rate constant of ∼3 s−1. Similar effects were seen in cells taken from sheep in which heart failure had been induced by rapid pacing. The decrease of Ca transient amplitude was accompanied by a decrease of SR Ca content. During this phase, the maximum (end-diastolic) SR Ca content fell while the minimum systolic increased.ConclusionsThis study shows that, under conditions designed to be as physiological as possible, potentiation of RyR opening has no maintained effect on the systolic Ca transient. This result makes it unlikely that potentiation of the RyR has a maintained role in positive inotropy.

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Section: Introductionmentioning

confidence: 99%

Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions

Greensmith

Galli

Trafford

et al. 2014

Cardiovascular Research

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“…This proposal has not been effectively countered by studies on ventricular myocytes, which exclusively express RyR2. This is due to the fact that the principal regulatory effect of cADPR with respect to RyR2 is to increase the sensitivity of this RyR subtype to Ca 2ϩ -induced Ca 2ϩ release (8,9), and in light of the fact that the sensitivity of RyRs to Ca 2ϩ -induced Ca 2ϩ release may be augmented by an increase in Ca 2ϩ concentration within the cytoplasm and/or S/ER lumen (15).…”

Section: Intracellular Camentioning

confidence: 99%

“…Although a wealth of evidence across a variety of cell types (3)(4)(5)(6)(7)(8)(9) supports the original proposal that cADPR activates RyRs (10), studies on reconstituted RyRs in lipid bilayers have failed to conclusively demonstrate direct regulation of these channels by cADPR (11), and it has been suggested that cADPR may initiate Ca 2ϩ signals via RyRs and IP 3 Rs by promoting Ca 2ϩ uptake into the S/ER by S/ER Ca 2ϩ ATPases (SERCA) (12)(13)(14). This proposal has not been effectively countered by studies on ventricular myocytes, which exclusively express RyR2.…”

Section: Intracellular Camentioning

confidence: 99%

Cyclic Adenosine Diphosphate Ribose Activates Ryanodine Receptors, whereas NAADP Activates Two-pore Domain Channels

Ogunbayo

Zhu

Rossi

et al. 2011

Journal of Biological Chemistry

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The mechanism by which cyclic adenosine diphosphate ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) mobilize intracellular Ca 2؉ Intracellular Ca 2ϩ signals are initiated by Ca 2ϩ release from intracellular stores, and traditionally, the sarco/endoplasmic reticulum (S/ER) 2 has been considered to be the major releasable store. From this store, Ca 2ϩ may be released through the opening of inositol 1,4,5-trisphosphate receptors (IP 3 Rs) and/or ryanodine receptors (RyRs), the two groups of intracellular Ca 2ϩ release channels located on S/ER membranes. It is generally accepted that of the recognized Ca 2ϩ -mobilizing second messengers, inositol 1,4,5-trisphosphate facilitates this process by activating IP 3 Rs (1).By contrast, the mechanism by which the pyridine nucleotides cyclic adenosine diphosphate ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) (2) mobilize intracellular Ca 2ϩ stores remains controversial. Although a wealth of evidence across a variety of cell types (3-9) supports the original proposal that cADPR activates RyRs (10), studies on reconstituted RyRs in lipid bilayers have failed to conclusively demonstrate direct regulation of these channels by cADPR (11), and it has been suggested that cADPR may initiate Ca 2ϩ signals via RyRs and IP 3 Rs by promoting Ca 2ϩ uptake into the S/ER by S/ER Ca 2ϩ ATPases (SERCA) (12)(13)(14). This proposal has not been effectively countered by studies on ventricular myocytes, which exclusively express RyR2. This is due to the fact that the principal regulatory effect of cADPR with respect to RyR2 is to increase the sensitivity of this RyR subtype to Ca 2ϩ -induced Ca 2ϩ release (8, 9), and in light of the fact that the sensitivity of RyRs to Ca 2ϩ -induced Ca 2ϩ release may be augmented by an increase in Ca 2ϩ concentration within the cytoplasm and/or S/ER lumen (15).The mechanism by which NAADP triggers intracellular Ca 2ϩ release has also been hotly debated. We recently identified a family of two-pore domain channels (TPC1-3, TPCN1-3 for gene name) as endolysosome-targeted, NAADP-gated Ca 2ϩ release channels (16, 17), and our findings have since been confirmed by others (18,19

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“…cADPR is known to mobilize Ca 2+ from the SR Ca 2+ stores through the activation of ryanodine receptors (RyRs) in a wide range of cell types [16, 17]. Moreover, cADPR has been proposed to serve an additional role in activating the SERCA pump [18, 19]. However, the exact mechanism by which cADPR regulates SR Ca 2+ stores in skeletal muscle cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

CD38-cADPR-SERCA Signaling Axis Determines Skeletal Muscle Contractile Force in Response to β-Adrenergic Stimulation

Park

Nam

Kim

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cyclic ADP-ribose (cADPR) is a Ca²⁺ -mobilization messenger that acts on ryanodine-sensitive Ca²⁺ channels in the sarcoplasmic reticulum (SR) Ca²⁺ stores. Moreover, it has been proposed that cADPR serves an additional role in activating the sarcoendoplasmic reticulum Ca²⁺ -ATPase (SERCA) pump. The aim of this study was to determine the exact mechanism by which cADPR regulates SR Ca²⁺ stores in physiologically relevant systems. Methods: We analyzed Ca²⁺ signals as well as the production of Ca²⁺ mobilizing messengers in the skeletal muscle cells of mice subjected to intensive exercise or in the SR fractions from skeletal muscle cells after β-adrenergic receptor (β-AR) stimulation. Results: We show that cADPR enhances SERCA activity in skeletal muscle cells in response to β-AR agonists, increasing SR Ca²⁺ uptake. We demonstrate that cADPR is generated by CD38, a cADPR-synthesizing enzyme, increasing muscle Ca²⁺ signals and contractile force during exercise. CD38 is upregulated by the cAMP response element–binding protein (CREB) transcription factor upon β-AR stimuli and exercise. CD38 knockout (KO) mice show defects in their exercise and cADPR synthesis capabilities, lacking a β-AR agonist-induced muscle contraction when compared to wild-type mice. The skeletal muscle of CD38 KO mice exhibits delayed cytosolic Ca²⁺ clearance and reduced SERCA activity upon exercise. Conclusion: These findings provide insight into the physiological adaptive mechanism by which the CD38- cADPR-SERCA signaling axis plays an essential role in muscle contraction under exercise, and define cADPR as an endogenous activator of SERCA in enhancing the SR Ca²⁺ load.

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Dual effects of cyclic ADP-ribose on sarcoplasmic reticulum Ca2+ release and storage in cardiac myocytes isolated from guinea-pig and rat ventricle☆

Cited by 26 publications

References 38 publications

Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions

Direct measurements of SR free Ca reveal the mechanism underlying the transient effects of RyR potentiation under physiological conditions

Cyclic Adenosine Diphosphate Ribose Activates Ryanodine Receptors, whereas NAADP Activates Two-pore Domain Channels

CD38-cADPR-SERCA Signaling Axis Determines Skeletal Muscle Contractile Force in Response to β-Adrenergic Stimulation

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