© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Effect of 5-HT4 receptor stimulation on the pacemaker current If in human isolated atrial myocytes
aDepartment of Pharmacology, University of Firenze, Viale G.B. Morgagni 65, 50134 Firenze, Italy
bDepartment of Cardiosurgery, Azienda Ospedaliera Careggi, Firenze, Italy
* Corresponding author. Tel.: +39-(55)-427-1264; fax: +39-(55)-427-1285; e-mail: mugelli@server1.pharm.unifi.it
Objective: 5-HT4 receptors are present in human atrial cells and their stimulation has been implicated in the genesis of atrial arrhythmias including atrial fibrillation. An If-like current has been recorded in human atrial myocytes, where it is modulated by ß-adrenergic stimulation. In the present study, we investigated the effect of serotonin (5-hydroxytryptamine, 5-HT) on If electrophysiological properties, in order to get an insight into the possible contribution of If to the arrhythmogenic action of 5-HT in human atria. Methods: Human atrial myocytes were isolated by enzymatic digestion from samples of atrial appendage of patients undergoing corrective cardiac surgery. Patch-clamped cells were superfused with a modified Tyrode's solution in order to amplify If and reduce overlapping currents. Results and conclusions: A time-dependent, cesium-sensitive increasing inward current, that we had previously described having the electrophysiological properties of the pacemaker current If, was elicited by negative steps (–60 to –130 mV) from a holding potential of –40 mV. Boltzmann fit of control activation curves gave a midpoint (V1/2) of –88.9±2.6 mV (n=14). 5-HT (1 µM) consistently caused a positive shift of V1/2 of 11.0±2.0 mV (n=8, p<0.001) of the activation curve toward less negative potentials, thus increasing the amount of current activated by clamp steps near the physiological maximum diastolic potential of these cells. The effect was dose-dependent, the EC50 being 0.14 µM. Maximum current amplitude was not changed by 5-HT. 5-HT did not increase If amplitude when the current was maximally activated by cAMP perfused into the cell. The selective 5-HT4 antagonists, DAU 6285 (10 µM) and GR 125487 (1 µM), completely prevented the effect of 5-HT on If. The shift of V1/2 caused by 1 µM 5-HT in the presence of DAU 6285 or GR 125487 was 0.3±1 mV (n=6) and 1.0±0.6 mV (n=5), respectively (p<0.01 versus 5-HT alone). The effect of 5-HT4 receptor blockade was specific, since neither DAU 6285 nor GR 125487 prevented the effect of 1 µM isoprenaline on If. Thus, 5-HT4 stimulation increases If in human atrial myocytes; this effect may contribute to the arrhythmogenic action of 5-HT in the human atrium.
KEYWORDS Human atrial myocytes; Serotonin (5-HT); 5-HT4 receptor subtype; Arrhythmia (mechanisms); Pacemaker current
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Severi, C. Corsi, and E. Cerbai From in vivo plasma composition to in vitro cardiac electrophysiology and in silico virtual heart: the extracellular calcium enigma Phil Trans R Soc A, June 13, 2009; 367(1896): 2203 - 2223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Liu, M. S. Geddis, Y. Wen, W. Setlik, and M. D. Gershon Expression and function of 5-HT4 receptors in the mouse enteric nervous system Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G1148 - G1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bianchi, O. Kunduzova, E. Masini, C. Cambon, D. Bani, L. Raimondi, M.-H. Seguelas, S. Nistri, W. Colucci, N. Leducq, et al. Oxidative Stress by Monoamine Oxidase Mediates Receptor-Independent Cardiomyocyte Apoptosis by Serotonin and Postischemic Myocardial Injury Circulation, November 22, 2005; 112(21): 3297 - 3305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. I. Leftheriotis, G. N. Theodorakis, D. Poulis, P. G. Flevari, E. G. Livanis, E. K. Iliodromitis, A. Papalois, and D. Th. Kremastinos The effects of 5-HT4 receptor blockade and stimulation, during six hours of atrial fibrillation Europace, January 1, 2005; 7(6): 560 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lonardo, E. Cerbai, S. Casini, G. Giunti, M. Bonacchi, F. Battaglia, B. Fiorani, P. L. Stefano, G. Sani, and A. Mugelli Atrial natriuretic peptide modulates the hyperpolarization-activated current (If) in human atrial myocytes Cardiovasc Res, August 15, 2004; 63(3): 528 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Barrere-Lemaire, C. Piot, F. Leclercq, J. Nargeot, and S. Richard Facilitation of L-type calcium currents by diastolic depolarization in cardiac cells: impairment in heart failure Cardiovasc Res, August 1, 2000; 47(2): 336 - 349. [Abstract] [Full Text] [PDF]
|
|