Removal of Mg<sup>2+</sup> inhibition of cardiac ryanodine receptor by palmitoyl coenzyme A

Connelly, Timothy; Ahern, Christopher A.; Sukhareva, Manana; Coronado, Roberto

doi:10.1016/0014-5793(94)00969-4

Cited by 13 publications

(12 citation statements)

References 19 publications

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“…In our hands caffeine caused only a small transient response, so we could not deplete the CICR pool and test cross-desensitization. Fulceri et al (29) in skeletal muscle and Coronado and colleagues (23,24) in both skeletal and cardiac muscle, found that palmitoyl-CoA could increase ryanodine binding (increased binding is taken to be an indicator of the channel's open state, for review, see Ref. 6), and the acyl derivatives could increase the Ca 2ϩ channel open probability.…”

Section: Discussionmentioning

confidence: 99%

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Acyl-Coenzyme A Causes Ca2+ Release in Pancreatic Acinar Cells

Fitzsimmons

McRoberts

Tachiki

et al. 1997

Journal of Biological Chemistry

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Cytosolic Ca 2ϩ is an important regulator of many cell functions. Increases in cytosolic Ca 2ϩ occur by release of Ca 2ϩ from intracellular stores located in the endoplasmic reticulum. There are at least two types of Ca 2ϩ channels that regulate release from Ca 2ϩ stores: an inositol 1,4,5-trisphosphate (IP 3 ) 1 -sensitive channel (IP 3 receptor) and a ryanodine-sensitive channel (ryanodine receptor). As its name implies, IP 3 opens the IP 3 receptor and is used as a second messenger in many cells to release Ca 2ϩ . The ryanodine-sensitive channel (RyR) is responsible for calcium-induced calcium release (CICR).There is solid evidence for CICR in the pancreatic acinar cell (1, 2), in addition to some of the first evidence for IP 3 signaling (3). CICR is important in the acinar cell during submaximal agonist stimulation. Low doses of cholecystokinin or carbachol induce Ca 2ϩ waves and oscillations (4). In the two pool model of oscillations, IP 3 acts as an initiator of Ca 2ϩ release triggering CICR, generating the Ca 2ϩ spike (5). Discovery of regulators of CICR are important for full understanding of Ca 2ϩ signaling. There is a growing list of RyR regulators including, caffeine, cyclic ADP-ribose, procaine, spermine, and long chain acyl-CoA derivatives (6). Even though CICR has been established for the pancreatic acinar cell, there is conflicting data regarding the effects of ryanodine and caffeine (classic activators of the RyR). In rat pancreatic acinar cells, there is data supporting activation (7), inhibition (8), and lack of effect (2) of ryanodine and/or caffeine. Unlike ryanodine and caffeine, cyclic ADP-ribose, another activator of the RyR, is naturally occurring in many cell types, but some mammalian cells, including pancreatic acinar cells, are far less sensitive to cADPR than sea urchin eggs (9). Acyl-CoA are also naturally occurring compounds that release Ca 2ϩ (10), but there is no data regarding the presence or the effects of acyl-CoA on acinar cell Ca 2ϩ movements. To study the regulation of CICR in pancreas, we tested the effect of acyl-CoA on Ca 2ϩ release mechanisms in permeablized rat pancreatic acini. Also the effect of acyl-CoA in relation to those of ryanodine and caffeine was measured. EXPERIMENTAL PROCEDURESIsolation of Acini-Rat pancreatic acini were isolated as described previously (11). The rats were sacrificed by CO 2 induced asphyxiation, followed by cervical dislocation. The pancreas was removed and injected with a collagenase, digestion buffer (in mM: 95 NaCl, 6 KCl, 1 MgCl 2 , 4 sodium pyruvate, 11 glucose, 2 NaH 2 PO 4 , 4 sodium fumarate, 5 glutamate, 25 HEPES, 2 CaCl 2 , 2 glutamine, also included 20 units/ml purified collagenase, 2 ϫ minimal Eagle's amino acids, and 0.2% (w/v) bovine serum albumin (BSA) (pH 7.4) (NaOH)). The pancreas was incubated 45 min at 37°C in a shaking water bath (Dubnoff, Precision Scientific, Chicago, IL) in 5 ml of digestion buffer with three changes of buffer. Acini were dispersed by passage through large and small bore glass pipettes and then washed...

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Section: Discussionmentioning

confidence: 99%

“…Third, addition of palmitoyl-CoA to whole cells did not cause Ca 2ϩ to leak into the cells through a solublized plasma membrane. Finally, from data in the literature (23,24), detailed electrical recordings in lipid bilayer experiments could be performed in the presence of acyl-CoA (1-100 M).…”

Section: Discussionmentioning

confidence: 99%

Acyl-Coenzyme A Causes Ca2+ Release in Pancreatic Acinar Cells

Fitzsimmons

McRoberts

Tachiki

et al. 1997

Journal of Biological Chemistry

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“…The cells were loaded with the Ca# + -indicator dye, C ") -Calcium Green, which partitions into membranes, thus providing a Ca# + measurement in localized areas within the cell [26,27]. We used palmitoyl-CoA (an activator of Ca# + release from the RyR [16,17]) to activate Ca# + release through RyR. We found Ca# + release throughout the acinar cell ( Figure 6).…”

Section: Localization Of Ca 2 + Releasementioning

confidence: 99%

“…To resolve these discrepancies we performed RyR-isoformspecific RT-PCR, Western-blot analysis with different antibodies and microscopic Ca# + -release measurements with an activator of RyR, palmitoyl-CoA [16,17]. The results show that multiple forms of RyR are expressed in rat pancreatic acinar cells.…”

Section: Introductionmentioning

confidence: 99%

Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells

Fitzsimmons

Gukovsky

McRoberts

et al. 2000

Biochemical Journal

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Regulation of cytosolic Ca2+ is important for a variety of cell functions. The ryanodine receptor (RyR) is a Ca2+ channel that conducts Ca2+ from internal pools to the cytoplasm. To demonstrate the presence of the RyR in the pancreatic acinar cell, we performed reverse transcriptase (RT)-PCR, Western blot, immunocytochemistry and microscopic Ca2+-release measurements on these cells. RT-PCR showed the presence of mRNA for RyR isoforms 1, 2 and 3 in both rat pancreas and dispersed pancreatic acini. Furthermore, mRNA expression for RyR isoforms 1 and 2 was demonstrated by RT-PCR in individual pancreatic acinar cells selected under the microscope. Western-blot analysis of acinar cell immunoprecipitates, using antibodies against RyR1 and RyR2, showed a high-molecular-mass (> 250kDa) protein band that was much less intense when immunoprecipitated in the presence of RyR peptide. Functionally, permeablized acinar cells stimulated with the RyR activator, palmitoyl-CoA, released Ca2+ from both basolateral and apical regions. These data show that pancreatic acinar cells express multiple isoforms of the RyR and that there are functional receptors throughout the cell.

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“…Long-chain fatty acyl-CoAs accumulate when fatty acid uptake by the cell exceeds ␤-oxidation. These CoA derivatives can be used in the synthesis of ceramide, diacylglycerol, and triacylglycerol (lipid), in addition to directly affecting the activity of various proteins involved in metabolism (e.g., hexokinase), cellular signaling (e.g., specific protein kinase C isoforms), and calcium handling (e.g., ryanodine receptor) (39,43,44). It has been suggested that ceramide might cause contractile dysfunction in the ZDF rat through increased iNOS expression and induction of apoptosis (13).…”

Section: Fig 1 Myocardial Oxygen Consumption (A) Carbohydrate Oxidmentioning

confidence: 99%

Impaired Long-Chain Fatty Acid Oxidation and Contractile Dysfunction in the Obese Zucker Rat Heart

et al. 2002

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We investigated whether decreased responsiveness of the heart to physiological increases in fatty acid availability results in lipid accumulation and lipotoxic heart disease. Lean and obese Zucker rats were either fed ad libitum or fasted overnight. Fasting increased plasma nonesterified fatty acid levels in both lean and obese rats, although levels were greatest in obese rats regardless of nutritional status. Despite increased fatty acid availability, the mRNA transcript levels of peroxisome proliferator-activated receptor (PPAR)-␣-regulated genes were similar in fed lean and fed obese rat hearts. Fasting increased expression of all PPAR-␣-regulated genes in lean Zucker rat hearts, whereas, in obese Zucker rat hearts, muscle carnitine palmitoyltransferase and medium-chain acyl-CoA dehydrogenase were unaltered with fasting. Rates of oleate oxidation were similar for hearts from fed rats. However, fasting increased rates of oleate oxidation only in hearts from lean rats. Dramatic lipid deposition occurred within cardiomyocytes of obese, but not lean, Zucker rats upon fasting. Cardiac output was significantly depressed in hearts isolated from obese rats compared with lean rats, regardless of nutritional status. Fasting increased cardiac output in hearts of lean rats only. Thus, the heart's inability to increase fatty acid oxidation in proportion to increased fatty acid availability is associated with lipid accumulation and contractile dysfunction of the obese Zucker rat.

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Removal of Mg²⁺ inhibition of cardiac ryanodine receptor by palmitoyl coenzyme A

Cited by 13 publications

References 19 publications

Acyl-Coenzyme A Causes Ca2+ Release in Pancreatic Acinar Cells

Acyl-Coenzyme A Causes Ca2+ Release in Pancreatic Acinar Cells

Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells

Impaired Long-Chain Fatty Acid Oxidation and Contractile Dysfunction in the Obese Zucker Rat Heart

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Removal of Mg2+ inhibition of cardiac ryanodine receptor by palmitoyl coenzyme A

Cited by 13 publications

References 19 publications

Acyl-Coenzyme A Causes Ca2+ Release in Pancreatic Acinar Cells

Acyl-Coenzyme A Causes Ca2+ Release in Pancreatic Acinar Cells

Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells

Impaired Long-Chain Fatty Acid Oxidation and Contractile Dysfunction in the Obese Zucker Rat Heart

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Removal of Mg²⁺ inhibition of cardiac ryanodine receptor by palmitoyl coenzyme A