β2-Adrenergic Receptor Signaling Acts via No Release to Mediate Ach-Induced Activation of Atp-Sensitive K+ Current in Cat Atrial Myocytes

Wang, Yong G.; Dedkova, Elena N.; Steinberg, Susan F.; Blatter, Lothar A.; Lipsius, Stephen L.

doi:10.1085/jgp.119.1.69

Cited by 22 publications

(52 citation statements)

References 48 publications

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“…We also sought to determine whether stim-ulation of muscarinic receptors increases NO i production via G i proteins coupled to phosphatidylinositol 3-kinase (PI-3K)/ protein kinase B (Akt) signaling, similar to NO i production elicited by ␤ 2 -adrenergic receptor (AR) stimulation. 19 The present results indicate that ACh exposure and withdrawal increase NO i production. ACh-induced increases in NO i require both muscarinic receptor-mediated G i /PI-3K/Akt signaling and voltage-activated Ca 2ϩ influx for stimulation of calmodulin (CaM)-dependent endothelial NO synthase (eNOS) activity.…”

supporting

confidence: 62%

Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes

Dedkova

Wang

et al. 2003

Circulation Research

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Abstract-Fluorescence microscopy and the NO-sensitive indicator 4,5-diaminofluorescein were used to determine the effects of acetylcholine (ACh) on intracellular NO (NO i ) in cat atrial myocytes. Field stimulation (1 Hz) of cells or exposure of quiescent cells to ACh (1 to 10 mol/L) had no effect on NO i . However, in field-stimulated cells, ACh exposure increased NO i , and ACh withdrawal elicited an additional, prominent increase in NO i production. During ACh exposure, addition of 1 mol/L atropine increased NO i production similar to ACh withdrawal. ACh-induced increases in NO i were reduced by prior exposure to 1 mmol/L extracellular Ca 2ϩ ([Ca 2ϩ ] o ) and prevented by 0. 8 However, ACh withdrawal stimulates I Ca,L above control levels, ie, rebound stimulation, and this response is mediated by NO signaling. 8,9 The rebound stimulation of I Ca,L elicited by ACh withdrawal results in stimulation of atrial contraction, 9 atrial pacemaker activity, 10 and the potential development of Ca 2ϩ -mediated delayed afterdepolarizations and arrhythmic atrial activity. 11 These findings are consistent with reports in multicellular atrial preparations that ACh withdrawal elicits rebound stimulation of intracellular Ca 2ϩ transients and contraction. 12 The fact that rebound stimulation is exhibited by multicellular tissue indicates that the stimulatory response to ACh withdrawal is not unique to isolated myocytes but rather is a physiological mechanism responsible for rapid recovery from cholinergic inhibition of atrial function. In both cat 8 and human 13 atrial myocytes, NO acts via cyclic GMP (cGMP)-induced inhibition of phosphodiesterase type III activity to increase endogenous cAMP levels. By this mechanism, NO signaling mediates the stimulation of I Ca,L elicited by ACh withdrawal. 8 These findings are consistent with studies in chick heart cells, in which ACh withdrawal stimulates cAMP above control levels. 14 Others laboratories have reported that ACh withdrawal stimulates I Ca,L in Purkinje fibers 15 and ventricular myocytes prestimulated by ␤-adrenergic agonists. 16,17 However, in contrast to atrial myocytes, the stimulatory effect of ACh withdrawal in ventricular myocytes is not mediated via NO or cGMP signaling 16,18 but rather is attributable to stimulation of adenylate cyclase by the ␤␥ subunit of G i protein. 16 In the present study, we used fluorescence microscopy and the NO-sensitive indicator DAF-2 to directly determine the effects of ACh on intracellular NO (NO i ) production in cat atrial myocytes. We also sought to determine whether stim-

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supporting

confidence: 62%

Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes

Dedkova

Wang

et al. 2003

Circulation Research

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“…We did observe a significant difference in vasodilator responses to isoproterenol infusion between Ado responders and nonresponders. Although isoproterenol does not work exclusively via cAMPmediated vasodilation (41), it has a strong cAMP component and may also evoke NO release. In this context, perhaps Ado responders have a greater cAMP component of Ado-mediated vasodilation perhaps resulting from stimulation of a greater number of G s stimulatory protein-mediated Ado receptor subtypes (Ado receptors A 2A and A 2B ), which are present on both endothelial and skeletal muscle cells (21).…”

Section: Discussionmentioning

confidence: 99%

Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia

Martin

Nicholson²,

Eisenach³

et al. 2006

Journal of Applied Physiology

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distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia. J Appl Physiol 101: [492][493][494][495][496][497][498][499] 2006. First published April 13, 2006; doi:10.1152/japplphysiol.00684.2005.-To gain insight into the role of adenosine (Ado) in exercise hyperemia, we compared forearm vasodilation induced by intra-arterial infusion of three doses of Ado with vasodilation during three workloads of forearm handgrip exercise in 27 human subjects. We measured forearm blood flow (FBF) using Doppler ultrasound and mean arterial pressure (MAP) via brachial artery catheters and calculated forearm vascular conductance (FVC ϭ FBF/MAP) during each infusion dose or workload. We found that about half of the subjects demonstrated robust vasodilator responsiveness to both Ado infusion and exercise, and the other half demonstrated blunted vasodilator responsiveness to Ado infusion compared with exercise. In 15 subjects (identified as "Ado responders"), the change in FVC above baseline was 209 Ϯ 33, 419 Ϯ 57, and 603 Ϯ 75 ml ⅐ min Ϫ1 ⅐ 100 mmHg Ϫ1 for the low, medium, and high doses of Ado, respectively, and 221 Ϯ 35, 413 Ϯ 54, and 582 Ϯ 70 ml ⅐ min Ϫ1 ⅐ 100 mmHg Ϫ1 for the low, medium, and high exercise workloads, respectively. In the other 12 subjects (identified as "Ado nonresponders"), the change in FVC above baseline was 102 Ϯ 36, 113 Ϯ 42, and 151 Ϯ 54 ml ⅐ min Ϫ1 ⅐ 100 mmHg Ϫ1 for the low, medium, and high doses of Ado, respectively (P Ͻ 0.05 vs. Ado responders), whereas exercise hyperemia was not different from Ado responders (P Ͼ 0.05). Furthermore, infusion of N G -monomethyl-Larginine (L-NMMA) blunted vasodilator responses to Ado infusion only in Ado responders (P Ͻ 0.01 vs. post-L-NMMA) and had no effect on exercise in either group. We also found differences in vasodilator responses to isoproterenol at all doses, but acetylcholine only at one dose, between Ado responders and nonresponders. We conclude that vasodilator responsiveness to Ado exhibits a bimodal distribution among human subjects involving differences in the contribution of nitric oxide to Ado-mediated vasodilation. Finally, our data support the concept that neither Ado nor nitric oxide is obligatory for exercise hyperemia.skeletal muscle blood flow; isoproterenol; acetylcholine; reactive hyperemia; N G -monomethyl-L-arginine MUSCLE BLOOD FLOW INCREASES dramatically during dynamic exercise. However, the main vasodilators that contribute to exercise hyperemia and their interactions remain uncertain (16,33,35). Possible contributors include, among others, adenosine (Ado) and related compounds. Studies in animals have both supported and rejected a role of Ado in exercise hyperemia. Some studies have demonstrated an increase in Ado concentration in venous blood (7) and/or an increase in interstitial Ado concentration in skeletal muscle (1, 39) during muscle contraction. In contrast, other studies failed to show any increase in venous Ado concentration (1, 39) or skeletal muscl...

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“…37 Although the positive inotropic action of ISO in the rat atrium is reported to be entirely accounted for by β 1 -adrenoceptors, a role for β 2 -adrenoceptors in atrial K ATP channel activation cannot be entirely ruled out. 37,38 Conversely, β 3 -adrenoceptors are negatively inotropic in the rat heart and may have attenuated the ISO-induced metabolic-stress. 39 …”

Section: Mechanism Of Atrial K Atp Channel Activationmentioning

confidence: 99%

Activation of Glibenclamide-Sensitive ATP-Sensitive K ⁺ Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia

Kim

Zhang

Khaliulin

et al. 2012

Circ: Arrhythmia and Electrophysiology

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β2-Adrenergic Receptor Signaling Acts via No Release to Mediate Ach-Induced Activation of Atp-Sensitive K+ Current in Cat Atrial Myocytes

Cited by 22 publications

References 48 publications

Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes

Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes

Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia

Activation of Glibenclamide-Sensitive ATP-Sensitive K ⁺ Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia

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β2-Adrenergic Receptor Signaling Acts via No Release to Mediate Ach-Induced Activation of Atp-Sensitive K+ Current in Cat Atrial Myocytes

Cited by 22 publications

References 48 publications

Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes

Signaling Mechanisms That Mediate Nitric Oxide Production Induced by Acetylcholine Exposure and Withdrawal in Cat Atrial Myocytes

Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia

Activation of Glibenclamide-Sensitive ATP-Sensitive K + Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia

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Activation of Glibenclamide-Sensitive ATP-Sensitive K ⁺ Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia