Store-Operated Cation Channels in the Heart and Cells of the Cardiovascular System

Freichel, Marc; Schweig, Ulli; Stauffenberger, Sibylle; Freise, Doris; Schorb, W; Flockerzi, Veit

doi:10.1159/000016321

Cited by 57 publications

(47 citation statements)

References 112 publications

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“…These results suggest that increased Ca 2+ influx by LTCCs was pathologic, consistent with our results here showing exacerbated hypertrophy following TAC stimulation or isoproterenol infusion in β2a DTG mice (Supplemental Figure 3). Similarly, increased Ca 2+ influx in myocytes through transient receptor potential canonical (TRPC) channels, which mediate store-, receptor-, and stretch-operated Ca 2+ entry (28)(29)(30)(31), can induce pathologic hypertrophy through a calcineurin-dependent pathway (32)(33)(34). Similarly, we have shown that overexpression of PMCA4b, which presumably removes Ca 2+ from defined sarcolemmal microdomains involved in signaling to calcineurin, could reduce the cardiac hypertrophic response (9).…”

Section: Discussionmentioning

confidence: 80%

α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

Nakayama

Bódi²,

Correll³

et al. 2009

J. Clin. Invest.

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In noncontractile cells, increases in intracellular Ca 2+ concentration serve as a second messenger to signal proliferation, differentiation, metabolism, motility, and cell death. Many of these Ca 2+ -dependent regulatory processes operate in cardiomyocytes, although it remains unclear how Ca 2+ serves as a second messenger given the high Ca 2+ concentrations that control contraction. T-type Ca 2+ channels are reexpressed in adult ventricular myocytes during pathologic hypertrophy, although their physiologic function remains unknown. Here we generated cardiac-specific transgenic mice with inducible expression of α1G, which generates Ca v 3.1 current, to investigate whether this type of Ca 2+ influx mechanism regulates the cardiac hypertrophic response. Unexpectedly, α1G transgenic mice showed no cardiac pathology despite large increases in Ca 2+ influx, and they were even partially resistant to pressure overload-, isoproterenol-, and exercise-induced cardiac hypertrophy. Conversely, α1G -/-mice displayed enhanced hypertrophic responses following pressure overload or isoproterenol infusion. Enhanced hypertrophy and disease in α1G -/-mice was rescued with the α1G transgene, demonstrating a myocyte-autonomous requirement of α1G for protection. Mechanistically, α1G interacted with NOS3, which augmented cGMP-dependent protein kinase type I activity in α1G transgenic hearts after pressure overload. Further, the anti-hypertrophic effect of α1G overexpression was abrogated by a NOS3 inhibitor and by crossing the mice onto the Nos3 -/-background. Thus, cardiac α1G reexpression and its associated pool of T-type Ca 2+ antagonize cardiac hypertrophy through a NOS3-dependent signaling mechanism.

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Section: Discussionmentioning

confidence: 80%

α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

Nakayama

Bódi²,

Correll³

et al. 2009

J. Clin. Invest.

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“…Voltage-independent SOC channels are sensitive to changes in SR Ca 2ϩ content and are activated upon SR depletion. TRPC gene products have been suggested as potential underlying components of native SOC in the cardiovascular system (16,39,43). TRPC1, TRPC4, and TRPC6 figure prominently as components of native SOC in pulmonary VSMC and endothelial cells and are involved in regulating vascular tone, microvascular permeability, and cell proliferation (5,13,17,21,33,40,61,62,68,70,72).…”

Section: Discussionmentioning

confidence: 99%

ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells

Zhang¹,

Remillard²,

Fantozzi³

et al. 2004

American Journal of Physiology-Cell Physiology

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. ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 287: C1192-C1201, 2004. First published June 30, 2004 doi:10.1152/ajpcell.00158.2004.-Extracellular ATP and intracellular cyclic AMP response element-binding protein (CREB, a transcription factor) promote cell proliferation in many cell types. The canonical transient receptor potential (TRPC) channels, which putatively participate in forming store-and receptor-operated Ca 2ϩ channels, have been implicated in the pulmonary vascular remodeling processes. A link between extracellular ATP, CREB activation, and TRPC4 channel expression and activity has not been shown in human pulmonary artery smooth muscle cells (PASMC). Long-term (24 -48 h) treatment of human PASMC with a low dose (100 M) of ATP, which did not trigger a transient rise in free cytosolic Ca 2ϩ concentration ([Ca 2ϩ ]i) when applied acutely to the cells, caused marked increases in CREB phosphorylation and TRPC4 protein expression. The time course indicated that the ATP-mediated CREB phosphorylation preceded TRPC4 upregulation, whereas transfection of a nonphosphorylatable CREB mutant abolished ATP-mediated TRPC4 expression. Furthermore, treatment of human PASMC with ATP also enhanced the amplitude of capacitative Ca 2ϩ entry (CCE) induced by passive store depletion, whereas the small interfering RNA specifically targeting TRPC4 attenuated ATP-mediated increases in TRPC4 expression and CCE amplitude and inhibited ATP-induced PASMC proliferation. These data suggest that low-dose ATP exerts part of its mitogenic effect in human PASMC via CREB-mediated upregulation of TRPC4 channel expression and activity and the subsequent increase in CCE and [Ca 2ϩ ]i.capacitative Ca 2ϩ entry; proliferation; vascular smooth muscle NUCLEOTIDES SUCH AS ATP, ADP, AND UTP act as extracellular messengers and play an important role in regulating vascular tone and cell proliferation and differentiation (12,18,25,41,56). Intracellular ATP is an essential molecular energy source, while extracellular ATP, which can be released from vascular endothelial cells (44, 71), damaged vessel walls (4), hypoxic myocardium (15), and aggregating platelets (29), serves as a potent vasoconstrictor (20, 24) and smooth muscle and endothelial cell mitogen (7,19). ATP also can be released from perivascular nerves as an excitatory neurotransmitter (6). The contractile and mitogenic effects of extracellular ATP on vascular smooth muscle cells (VSMC) are mediated by activation of a family of G protein-coupled receptors, P 2 purinoceptors (including at least 6 subtypes: P 2X , P 2Y , P 2T , P 2U , P 2Z , and P 2D ), which are linked to phospholipases and adenylate cyclase (7, 65). Activation of P 2 purinoceptors by ATP and UTP (24) in pulmonary artery smooth muscle cells (PASMC) causes pulmonary vasoconstriction and in fibroblasts promotes the progression of pulmonary vascular remodeling by stimulating f...

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“…Specific primers for mTRPC1, mTRPC2, mTRPC3, mTRPC4, mTRPC5, mTRPC6, and mTRPC7 were used for PCR amplification, respectively. 19 To control for potential genomic DNA contamination, a cDNA reaction was performed but in the absence of reverse transcriptase and used as template for PCR reactions. …”

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confidence: 99%

Store-Operated Ca ²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

Chu

Chaulet

et al. 2007

Circulation Research

122

108

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Abstract-Store-operated Ca 2ϩ entry was investigated in isolated mouse sinoatrial nodes (SAN) dissected from right atria and loaded with Ca 2ϩ indicators. Incubation of the SAN in Ca 2ϩ -free solution caused a substantial decrease in resting intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) and stopped pacemaker activity. Reintroduction of Ca 2ϩ in the presence of cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca 2ϩ pump inhibitor, led to sustained elevation of [Ca 2ϩ ] i , a characteristic of store-operated Ca 2ϩ channel (SOCC) activity. Two SOCC antagonists, Gd 3ϩ and SKF-96365, inhibited 72Ϯ8% and 65Ϯ8% of this Ca 2ϩ influx, respectively. SKF-96365 also reduced the spontaneous pacemaker rate to 27Ϯ4% of control in the presence of CPA. Because members of the transient receptor potential canonical (TRPC) gene family may encode SOCCs, we used RT-PCR to examine mRNA expression of the 7 known mammalian TRPC isoforms. Transcripts for TRPC1, 2, 3, 4, 6, and 7, but not TRPC5, were detected. Immunohistochemistry using anti-TRPC1, 3, 4, and 6 antibodies revealed positive labeling in the SAN region and single pacemaker cells. 4,5 In ventricular myocytes, PLC responses are generally modest with only small amounts of IP 3 being produced. 6 Thus release of Ca 2ϩ through IP 3 R is probably too small to modify excitation-contraction coupling. However, atria myocytes express functional IP 3 R at 6 to 10 times higher levels than those in ventricules, and Ca 2ϩ release from IP 3 R may be involved in the generation of arrhythmias. 7 Furthermore, recent studies have shown that activation of PLC in the heart leads to Ca 2ϩ release from perinuclear IP 3 R and thereby regulates nuclear-cytoplasmic cycling of transcription factors and alters gene expression. 8 A similar role may be played by IP 3 and the IP 3 R in skeletal muscle and SOCCs have been implicated in IGF-1 induced muscle hypertrophy. 5,9 The identity of the genes that encode SOCCs remains uncertain. Studies of the transient receptor potential (TRP) gene from Drosophila showed that it encodes a PLC-activated Ca 2ϩ permeable channel. 10 Subsequently, 7 TRP channel homologues in mammals, termed TRPC1-TRPC7, have been identified and there is considerable evidence to indicate that TRPC1 can encode a SOCC. 11 In addition, a recent study showed that overexpression of TRPC3 substantially enhanced SOCC activity in the heart. 5 The importance of Ca 2ϩ release from stores in cardiac pacemaking is now widely accepted. [12][13][14] In a previous study, we found that activation of the P2Y 1 purinergic receptor by ATP results in modulation of pacemaker firing attirbutable to receptor-coupled PLC activation and depletion of SR Ca 2ϩ stores. 15 Because activation of SOCCs also involves PLC, we speculated that SOCCs might be present in pacemaker tissue.In mammals, the sinoatrial node (SAN) is a heterogeneous tissue. The shape of the action potential and the rate of rise of the pacemaker potential change progressively from the periphery to the center, the latter being the leadin...

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Store-Operated Cation Channels in the Heart and Cells of the Cardiovascular System

Cited by 57 publications

References 112 publications

α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells

Store-Operated Ca ²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

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Store-Operated Cation Channels in the Heart and Cells of the Cardiovascular System

Cited by 57 publications

References 112 publications

α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

α1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice

ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells

Store-Operated Ca 2+ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

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Store-Operated Ca ²⁺ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node