Copyright © 2006, European Society of Cardiology
Adenosine A2A receptors are expressed in human atrial myocytes and modulate spontaneous sarcoplasmic reticulum calcium release
aCell Physiology Laboratory, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Institut Catalá de Ciencies Cardiovasculars, Universitat Autònoma de Barcelona, St Antoni Ma Claret 167, 08025 Barcelona, Spain
bDepartment of Biochemistry and Molecular Biology, Universidad de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain
* Corresponding author. Tel.: +34 935565620; fax: +34 935565603. Email address: lhove{at}santpau.es
Background: Alterations in the cyclic AMP-dependent regulation of the cardiac ryanodine receptor (RyR2) have been proposed to account for increased spontaneous calcium release from the sarcoplasmic reticulum (SR) in patients with heart failure, ventricular tachyarrhythmias and atrial fibrillation. While the adenosine A2A receptor (A2AR) is known to regulate cyclic AMP levels, expression and function of this receptor in human cardiac myocytes has not been investigated.
Methods: PCR, western blotting and immunofluorescence were used to identify the A2AR, and functional effects of A2AR stimulation were measured with confocal calcium imaging and patch-clamp technique.
Results: The A2AR is expressed in the human right atrium and distributed in a banded pattern along the Z-lines, overlapping with the ryanodine receptor. A2AR stimulation caused a protein kinase A dependent increase in spontaneous SR calcium release in isolated human atrial myocytes. The A2AR agonist CGS21680 increased the frequency of calcium sparks from 0.12±0.03 to 0.31±0.08 sparks·µm min–1 (p<0.05) and calcium waves from 0.65±0.31 to 5.11±1.84 waves·min–1 (p<0.03). Moreover, spontaneous Na–Ca exchange currents (INCX) increased from 1.19±0.17 to 2.50±0.42 min–1 (p<0.001). In contrast, CGS21680 did not alter caffeine inducible calcium release (6.98±0.52 vs. 6.82±0.57 amol pF–1, p=0.6) or the spontaneous INCX amplitude (0.32±0.05 vs. 0.29±0.04 pA pF–1, p=0.2). Current–voltage relationship and amplitude of the L-type calcium current (1.62±0.18 vs. 1.80±0.18 pA pF–1) were not altered, but calcium release dependent inactivation was faster with CGS21680 (13.4±0.7 vs. 15.8±1.0 ms, p<0.001).
Conclusions: Adenosine A2A receptors are expressed in the human atrial myocardium and modulate the frequency of spontaneous calcium release from the SR.
KEYWORDS Adenosine; Arrhythmia (mechanisms); Calcium channel; e–c coupling; SR (function)
1 These authors contributed equally to this work.
Time for primary review 21 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. J. Chorro, I. Trapero, L. Such-Miquel, F. Pelechano, L. Mainar, J. Canoves, A. Tormos, A. Alberola, L. Hove-Madsen, J. Cinca, et al. Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1860 - H1869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, Y. Zhang, W. G. Wier, X. Yu, M. Zhao, H. Hu, L. Sun, X. He, Y. Wang, B. Wang, et al. Role of store-operated Ca2+ entry in adenosine-induced vasodilatation of rat small mesenteric artery Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H347 - H354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hasko and P. Pacher A2A receptors in inflammation and injury: lessons learned from transgenic animals J. Leukoc. Biol., March 1, 2008; 83(3): 447 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Venetucci, S.C. O'Neill, and D.A. Eisner Does the adenosine A2A receptor stimulate the ryanodine receptor? Cardiovasc Res, January 1, 2007; 73(1): 247 - 248. [Full Text] [PDF]
|
|
|
|
|
|
L. Hove-Madsen, C. Prat-Vidal, A. Llach, F. Ciruela, V. Casado, C. Lluis, A. Bayes-Genis, J. Cinca, and R. Franco Reply: Does the adenosine A2A receptor stimulate the ryanodine receptor? Cardiovasc Res, January 1, 2007; 73(1): 249 - 250. [Full Text] [PDF]
|
|