Laminin enhances β2‐adrenergic receptor stimulation of L‐type Ca2+ current via cytosolic phospholipase A2 signalling in cat atrial myocytes

Pabbidi, Malikarjuna R.; Ji, Xiang; Samarel, Allen M.; Lipsius, Stephen L.

doi:10.1113/jphysiol.2009.179226

Cited by 7 publications

(18 citation statements)

References 40 publications

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“…CytoD has been reported to interfere with multiple signaling pathways, though not with baseline Ca 2+ handling, 51 and effects of CytoD are mostly assigned to its action on the cytoskeleton. We currently do not have complementary tools for studying the role of the cytoskeleton, because, for example, colchicine reportedly affects baseline Ca 2+ transport.…”

Section: Limitationsmentioning

confidence: 99%

Selective Modulation of Coupled Ryanodine Receptors During Microdomain Activation of Calcium/Calmodulin-Dependent Kinase II in the Dyadic Cleft

Dries

Bito

Lenaerts

et al. 2013

Circulation Research

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Section: Limitationsmentioning

confidence: 99%

Selective Modulation of Coupled Ryanodine Receptors During Microdomain Activation of Calcium/Calmodulin-Dependent Kinase II in the Dyadic Cleft

Dries

Bito

Lenaerts

et al. 2013

Circulation Research

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“…For specific stimulation of ␤ 1-AR-dependent signaling (␤ 1-AR stimulation), cells were treated with ISO (0.1 M) in combination with the ␤ 2-AR subtype blocker ICI-118,551 (0.01 M). Simultaneous activation of ␤ 2/Gi and ␤2/Gs signaling (␤2-AR stimulation) was achieved with the combination of ISO (0.1 M) and the specific ␤ 1-AR inhibitor atenolol (0.01 M), whereas for selective ␤ 2/Gs stimulation, fenoterol (41,42) was used (0.1 M). Concentrations were chosen based on our previous studies (10, 51) on ␤-AR signaling in cat atrial myocytes.…”

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confidence: 99%

Regulation of cardiac alternans by β-adrenergic signaling pathways

Florea

Blatter

2012

American Journal of Physiology-Heart and Circulatory Physiology

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In cat atrial myocytes, β-adrenergic receptor (β-AR) stimulation exerts profound effects on excitation-contraction coupling and cellular Ca(2+) cycling that are mediated by β(1)- and β(2)-AR subtypes coupled to G proteins (G(s) and G(i)). In this study, we determined the effects of β-AR stimulation on pacing-induced Ca(2+) alternans. Ca(2+) alternans was recorded from single cat atrial myocytes with the fluorescent Ca(2+) indicator indo-1. Stable Ca(2+) alternans occurred at an average pacing frequency of 1.7 Hz at room temperature with a mean alternans ratio of 0.43. Nonselective β-AR stimulation as well as selective stimulation of β(1)/G(s), β(2)/G(s) + G(i), and β(2)/G(s) coupled pathways all abolished pacing-induced Ca(2+) alternans. β(1)-AR stimulation abolished alternans through stimulation of PKA and Ca(2+)/calmodulin-dependent protein kinase II, whereas β(2)-AR stimulation exclusively involved PKA and was mediated via G(s), whereas a known second pathway in cat atrial myocytes acting through G(i) and nitric oxide production was not involved in alternans regulation. Inhibition of various mitochondrial functions (dissipation of the mitochondrial membrane potential or inhibition of mitochondrial F(1)/F(0)-ATP synthase, mitochondrial Ca(2+) uptake via the mitochondrial Ca(2+) uniporter, and Ca(2+) extrusion via mitochondrial Na(+)/Ca(2+) exchange) enhanced Ca(2+) alternans; however, β-AR stimulation still abrogated alternans, provided that sufficient cellular ATP was available. Selective inhibition of mitochondrial or glycolytic ATP production did not prevent β-AR stimulation from abolishing Ca(2+) alternans. However, when both ATP sources were depleted, β-AR stimulation failed to decrease Ca(2+) alternans. These results indicate that in atrial myocytes, β-AR stimulation protects against pacing-induced alternans by acting through parallel and complementary signaling pathways.

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“…Cell attachment to LMN decreases β 1 -AR signaling by inhibiting adenylate cyclase activity and diminishing cAMP levels via integrin-dependent activation of focal adhesion kinase (FAK)/phosphatidyinositol-3’ kinase (PI-3K)/protein kinase B (Akt) signaling [2]. We also reported that atrial cell attachment to LMN enhances β 2 -AR signaling by activating Gi/ERK/cytosolic phospholipase A 2 (cPLA 2 )/arachidonic acid (AA) stimulation of I Ca,L [ 3 ]. β 2 -AR activation of cPLA 2 signaling is dependent on concomitant LMN-mediated inhibition of adenylate cyclase/cAMP-dependent kinase (PKA) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…We also reported that atrial cell attachment to LMN enhances β 2 -AR signaling by activating Gi/ERK/cytosolic phospholipase A 2 (cPLA 2 )/arachidonic acid (AA) stimulation of I Ca,L [ 3 ]. β 2 -AR activation of cPLA 2 signaling is dependent on concomitant LMN-mediated inhibition of adenylate cyclase/cAMP-dependent kinase (PKA) [ 3 ]. In other words, cell attachment to LMN acts via inhibition of adenylate cyclase/PKA to both inhibit β 1 -AR signaling and enhance β 2 -AR signaling through activation of cPLA 2 .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes

Pabbidi

Maxwell

et al. 2016

PLoS ONE

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We previously reported in atrial myocytes that inhibition of cAMP-dependent protein kinase (PKA) by laminin (LMN)-integrin signaling activates β2-adrenergic receptor (β2-AR) stimulation of cytosolic phospholipase A2 (cPLA2). The present study sought to determine the signaling mechanisms by which inhibition of PKA activates β2-AR stimulation of cPLA2. We therefore determined the effects of zinterol (0.1 μM; zint-β2-AR) to stimulate ICa,L in atrial myocytes in the absence (+PKA) and presence (-PKA) of the PKA inhibitor (1 μM) KT5720 and compared these results with atrial myocytes attached to laminin (+LMN). Inhibition of Raf-1 (10 μM GW5074), phospholipase C (PLC; 0.5 μM edelfosine), PKC (4 μM chelerythrine) or IP3 receptor (IP3R) signaling (2 μM 2-APB) significantly inhibited zint-β2-AR stimulation of ICa,L in–PKA but not +PKA myocytes. Western blots showed that zint-β2-AR stimulation increased ERK1/2 phosphorylation in–PKA compared to +PKA myocytes. Adenoviral (Adv) expression of dominant negative (dn) -PKCα, dn-Raf-1 or an IP3 affinity trap, each inhibited zint-β2-AR stimulation of ICa,L in + LMN myocytes compared to control +LMN myocytes infected with Adv-βgal. In +LMN myocytes, zint-β2-AR stimulation of ICa,L was enhanced by adenoviral overexpression of wild-type cPLA2 and inhibited by double dn-cPLA2S505A/S515A mutant compared to control +LMN myocytes infected with Adv-βgal. In–PKA myocytes depletion of intracellular Ca2+ stores by 5 μM thapsigargin failed to inhibit zint-β2-AR stimulation of ICa,L via cPLA2. However, disruption of caveolae formation by 10 mM methyl-β-cyclodextrin inhibited zint-β2-AR stimulation of ICa,L in–PKA myocytes significantly more than in +PKA myocytes. We conclude that inhibition of PKA removes inhibition of Raf-1 and thereby allows β2-AR stimulation to act via PKCα/Raf-1/MEK/ERK1/2 and IP3-mediated Ca2+ signaling to stimulate cPLA2 signaling within caveolae. These findings may be relevant to the remodeling of β-AR signaling in failing and/or aging heart, both of which exhibit decreases in adenylate cyclase activity.

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Laminin enhances β₂‐adrenergic receptor stimulation of L‐type Ca²⁺ current via cytosolic phospholipase A₂ signalling in cat atrial myocytes

Cited by 7 publications

References 40 publications

Selective Modulation of Coupled Ryanodine Receptors During Microdomain Activation of Calcium/Calmodulin-Dependent Kinase II in the Dyadic Cleft

Selective Modulation of Coupled Ryanodine Receptors During Microdomain Activation of Calcium/Calmodulin-Dependent Kinase II in the Dyadic Cleft

Regulation of cardiac alternans by β-adrenergic signaling pathways

Inhibition of cAMP-Dependent PKA Activates β2-Adrenergic Receptor Stimulation of Cytosolic Phospholipase A2 via Raf-1/MEK/ERK and IP3-Dependent Ca2+ Signaling in Atrial Myocytes

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