High Efficiency Activation of L-Type Ca<sup>2+</sup>Current by 5-HT in Human Atrial Myocytes

Scala, Emmanuella Di; Findlay, Ian; Rose, Stéphanie; Aupart, Michel; Argibay, Jorge; Cosnay, P; Bozon, Véronique

doi:10.3109/10606820490926115

Cited by 5 publications

(2 citation statements)

References 4 publications

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“…For example, increased activity of protein phosphatases in chronic AF has been shown to be associated with reduced basal and ISO-activated I CaL currents [18], and changes in protein phosphatases and/or kinases with AF could contribute to the reduced efficacy of 5-HT on I CaL current density. The ability of 5-HT to increase cyclic AMP and cyclic AMP-dependent protein kinase activity has been shown to be significantly less than that of ISO [6,19,20], although similar increases in I CaL were induced by 5-HT and ISO in atrial cells from patients in SR [8,19,21]. In addition, changes in the coupling of the stimulatory or inhibitory G-proteins with 5-HT or ISO receptors may differently affect adenylate cyclase activity leading to the phosphorylation/dephosphorylation of the L-type Ca 2+ channel [22,23].…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Pau

Workman

Kane

et al. 2007

Journal of Molecular and Cellular Cardiology

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5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT4 receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca2+ current (ICaL), action potential duration (APD) and arrhythmic activity at 37 °C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10 μM) produced an increase in ICaL of 115 ± 21% above control (n = 10 cells, 6 patients) that was significantly smaller than that in the SR group (232 ± 33%; p < 0.05; n = 27 cells, 12 patients). Subsequent co-application of isoproterenol (1 μM) caused a further increase in ICaL in the AF group (by 256 ± 94%) that was greater than that in the SR group (22 ± 6%; p < 0.05). The APD at 50% repolarisation (APD50) was prolonged by 14 ± 3 ms by 5-HT in the AF group (n = 37 cells, 14 patients). This was less than that in the SR group (27 ± 4 ms; p < 0.05; n = 58 cells, 24 patients). Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR group, but none was observed in the AF group (p < 0.05). Atrial fibrillation was associated with reduced effects of 5-HT, but not of isoproterenol, on ICaL in human atrial cells. This reduced effect on ICaL was associated with a reduced APD50 and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium.

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Section: Discussionmentioning

confidence: 99%

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Pau

Workman

Kane

et al. 2007

Journal of Molecular and Cellular Cardiology

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“…Thus, contrary to what happens with contraction, the PDE3 or PDE4 control on propensity of 5-HT-evoked arrhythmias on human atrial trabeculae from patients in sinus rhythm or with paroxysmal AF, is lost in persistent AF [93]. 5-HT stimulation has been shown to increase I f [94] and I Ca,L [91,94] in HAMs, but less than β-adrenergic stimulation [91,95] and without regulation of PDE3 or PDE4 [90].…”

Section: Autonomic Remodeling and Upregulation Of Sympathetic Signalingmentioning

confidence: 93%

Molecular Basis of Atrial Fibrillation Initiation and Maintenance

Beneke

Molina

2021

Hearts

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Atrial fibrillation (AF) is the most common cardiac arrhythmia, largely associated to morbidity and mortality. Over the past decades, research in appearance and progression of this arrhythmia have turned into significant advances in its management. However, the incidence of AF continues to increase with the aging of the population and many important fundamental and translational underlaying mechanisms remain elusive. Here, we review recent advances in molecular and cellular basis for AF initiation, maintenance and progression. We first provide an overview of the basic molecular and electrophysiological mechanisms that lead and characterize AF. Next, we discuss the upstream regulatory factors conducting the underlying mechanisms which drive electrical and structural AF-associated remodeling, including genetic factors (risk variants associated to AF as transcriptional regulators and genetic changes associated to AF), neurohormonal regulation (i.e., cAMP) and oxidative stress imbalance (cGMP and mitochondrial dysfunction). Finally, we discuss the potential therapeutic implications of those findings, the knowledge gaps and consider future approaches to improve clinical management.

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5-Hydroxytryptamine and atrial arrhythmogenesis: A “culprit mechanism” or bystander in patients with chronic atrial fibrillation?

Dobrev

2007

Journal of Molecular and Cellular Cardiology

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High Efficiency Activation of L-Type Ca²⁺Current by 5-HT in Human Atrial Myocytes

Cited by 5 publications

References 4 publications

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Molecular Basis of Atrial Fibrillation Initiation and Maintenance

5-Hydroxytryptamine and atrial arrhythmogenesis: A “culprit mechanism” or bystander in patients with chronic atrial fibrillation?

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High Efficiency Activation of L-Type Ca2+Current by 5-HT in Human Atrial Myocytes

Cited by 5 publications

References 4 publications

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

Molecular Basis of Atrial Fibrillation Initiation and Maintenance

5-Hydroxytryptamine and atrial arrhythmogenesis: A “culprit mechanism” or bystander in patients with chronic atrial fibrillation?

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High Efficiency Activation of L-Type Ca²⁺Current by 5-HT in Human Atrial Myocytes