Inositol 1,4,5-trisphosphate receptors and pacemaker rhythms

Ju, Yue-Kun; Woodcock, Elizabeth A.; Allen, David G.; Cannell, Mark B.

doi:10.1016/j.yjmcc.2012.06.004

Cited by 27 publications

(38 citation statements)

References 105 publications

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“…Compared with RyR, IP 3 R expression is scarce in ventricular myocytes, indicating a rather minor physiological role. While IP 3 R activation may be beneficial in that it serves as an inotropic support for ventricles, its predominant effect is to promote arrhythmias (56,57). To explain the increased arrhythmogenicity of IP 3 R stimulation, it has been suggested that Ca 2ϩ release via IP 3 Rs may activate additional currents such as the store-operated Ca 2ϩ currents or the Na ϩ /Ca 2ϩ exchange current (56).…”

Section: Discussionmentioning

confidence: 99%

“…While IP 3 R activation may be beneficial in that it serves as an inotropic support for ventricles, its predominant effect is to promote arrhythmias (56,57). To explain the increased arrhythmogenicity of IP 3 R stimulation, it has been suggested that Ca 2ϩ release via IP 3 Rs may activate additional currents such as the store-operated Ca 2ϩ currents or the Na ϩ /Ca 2ϩ exchange current (56). These currents may be partially responsible for the plateau phase of the Ca 2ϩ response elicited by extracellular application of LPI to cultured neonatal ventricular myocytes incubated with Ca 2ϩ -containing saline.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Deliu²,

Zhang

et al. 2013

Journal of Biological Chemistry

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Background:The LPI-sensitive receptor GPR55 signals through Ca 2ϩ . Results: Activation of sarcolemmal versus intracellular GPR55 mobilizes Ca 2ϩ from distinct pools and associates with cardiomyocyte depolarization and hyperpolarization, respectively. Conclusion: GPR55 location critically affects LPI-induced modulation of cardiomyocyte function. Significance: We identify GPR55 as a new receptor regulating cardiac function at two cellular sites.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Deliu²,

Zhang

et al. 2013

Journal of Biological Chemistry

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“…Ca 2+ released from the ER during cell stimulation modulates activities of effector molecules and is taken up by mitochondria to stimulate oxidative phosphorylation and enhance ATP production (4)(5)(6) to match energetic supply with enhanced demand. In addition, cells in vivo are constantly exposed to low levels of circulating hormones, transmitters, and growth factors that bind to plasma membrane receptors to provide a background level of cytoplasmic InsP 3 (7) that generates low-level stochastic InsP 3 R-mediated localized or propagating [Ca 2+ ] i signals (8)(9)(10). Such signals also play an important role in maintenance of cellular bioenergetics (8).…”

mentioning

confidence: 99%

Biphasic regulation of InsP ₃ receptor gating by dual Ca ²⁺ release channel BH3-like domains mediates Bcl-x _L control of cell viability

Yang

Vais

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Antiapoptotic Bcl-2 family members interact with inositol trisphosphate receptor (InsP 3 R) Ca 2+ release channels in the endoplasmic reticulum to modulate Ca 2+ signals that affect cell viability. However, the molecular details and consequences of their interactions are unclear. Here, we found that Bcl-x L activates single InsP 3 R channels with a biphasic concentration dependence. The Bcl-x L Bcl-2 homology 3 (BH3) domain-binding pocket mediates both high-affinity channel activation and low-affinity inhibition. Bcl-x L activates channel gating by binding to two BH3 domain-like helices in the channel carboxyl terminus, whereas inhibition requires binding to one of them and to a previously identified Bcl-2 interaction site in the channelcoupling domain. Disruption of these interactions diminishes cell viability and sensitizes cells to apoptotic stimuli. Our results identify BH3-like domains in an ion channel and they provide a unifying model of the effects of antiapoptotic Bcl-2 proteins on the InsP 3 R that play critical roles in Ca 2+ signaling and cell viability.T he inositol trisphosphate receptors (InsP 3 R) are a family of intracellular cation channels that release Ca 2+ from the endoplasmic reticulum (ER) in response to a variety of extracellular stimuli (1). Three InsP 3 R isoforms are ubiquitously expressed and regulate diverse cell processes, including cell viability (1). Activation of the channels by InsP 3 elicits changes in cytoplasmic Ca 2+ concentration ([Ca 2+ ] i ) that provide versatile signals to regulate molecular processes with high spatial and temporal fidelity (1). Regions of close proximity to mitochondria enable localized Ca 2+ release events to be transduced to mitochondria (2, 3). Ca 2+ released from the ER during cell stimulation modulates activities of effector molecules and is taken up by mitochondria to stimulate oxidative phosphorylation and enhance ATP production (4-6) to match energetic supply with enhanced demand. In addition, cells in vivo are constantly exposed to low levels of circulating hormones, transmitters, and growth factors that bind to plasma membrane receptors to provide a background level of cytoplasmic InsP 3 (7) that generates low-level stochastic InsP 3 R-mediated localized or propagating [Ca 2+ ] i signals (8-10). Such signals also play an important role in maintenance of cellular bioenergetics (8). Nevertheless, under conditions of cell stress the close proximity of mitochondria to Ca 2+ release sites may result in mitochondrial Ca 2+ overload and initiate Ca 2+ -dependent forms of cell death, including necrosis and apoptosis (11-13). It has been suggested that high levels of ER Ca 2+ (14-16) and enhanced activity of the InsP 3 R (17-19) promote cell death by providing a higher quantity of released Ca 2+ to mitochondria (3,20,21).Protein interactions modulate the magnitude and quality of InsP 3 R-mediated [Ca 2+ ] i signals that regulate apoptosis and cell viability. Notable in this regard is the Bcl-2 protein family. Proapoptotic Bcl-2-related proteins Bax ...

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“…Since some IP 3 Rs appear to be localized near the surface membrane, where TRPC3 is also located (Ju et al, , 2011, it is possible that Ca 2+ release via IP 3 Rs could interact with these ion channels in the surface membrane (and/or affect their trafficking). IP 3 R expression has been shown to increase in heart failure (Marks, 2000) and in atrial fibrillation (Yamada et al, 2002), which raises the possibility that this IP3-TRPC signaling system may become more important in pathological conditions Ju et al, 2012).…”

Section: Interaction Between Ip 3 R and Soce In Cardiac Pacemaker Tissuementioning

confidence: 99%

“…We also showed that type II IP 3 R are functionally expressed and affect Ca 2+ handling and pacemaker activity in the mouse SAN and whose activation would lead to store depletion (Ju et al, 2011(Ju et al, , 2012. The linkage between IP 3 R activation and SOCE has proven elusive, but a potential candidate, was found in HEK 293 cells expressing the Transient Receptor Potential Canonical-3 (TRPC3) channel (see below) (Kiselyov et al, 1998).…”

Section: Introduction the Role Of Intracellular Ca 2+ In Sinoatrial Amentioning

confidence: 95%

Ca2+ Signaling and Heart Rhythm

Lei¹,

Huang²,

Solaro³

et al. 2016

Frontiers Research Topics

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms Citation: Lee BH, Trajanovska S, Hao G, Allen DG, Lei M and Cannell MB (2015) The involvement of TRPC3 channels in sinoatrial arrhythmias. Front. Physiol. 6:86. doi: 10.3389/fphys.2015.00086 The involvement of TRPC3 channels in sinoatrial arrhythmias Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SAN). The association between AF and SAN dysfunction is probably related to the communication between the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker complex and/or pathological processes that affect both the SAN and atrial simultaneously. Recent evidence suggests that Ca 2+ entry through TRPC3 (Transient Receptor Potential Canonical-3) channels may underlie several pathophysiological conditions -including cardiac arrhythmias. However, it is still not known if atrial and sinoatrial node cells are also involved. In this article we will first briefly review TRPC3 and IP 3 R signaling that relate to store/receptor-operated Ca 2+ entry (SOCE/ROCE) mechanisms and cardiac arrhythmias. We will then present some of our recent research progress in this field. Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3 −/− mice) compared to wild type controls. We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP 3 R. Activation of G-protein coupled receptors (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca 2+ homeostasis changes in sinoatrial complex being linked to TRPC3. The results provide new evidence that TRPC3 may play a role in sinoatrial and atrial arrhythmias that are caused by GPCRs activation.

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Inositol 1,4,5-trisphosphate receptors and pacemaker rhythms

Cited by 27 publications

References 105 publications

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Biphasic regulation of InsP ₃ receptor gating by dual Ca ²⁺ release channel BH3-like domains mediates Bcl-x _L control of cell viability

Ca2+ Signaling and Heart Rhythm

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Inositol 1,4,5-trisphosphate receptors and pacemaker rhythms

Cited by 27 publications

References 105 publications

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Biphasic regulation of InsP 3 receptor gating by dual Ca 2+ release channel BH3-like domains mediates Bcl-x L control of cell viability

Ca2+ Signaling and Heart Rhythm

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Biphasic regulation of InsP ₃ receptor gating by dual Ca ²⁺ release channel BH3-like domains mediates Bcl-x _L control of cell viability