© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Localisation and functional significance of ryanodine receptors during β-adrenoceptor stimulation in the guinea-pig sino-atrial node
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK
* Corresponding author. Tel.: +44-1865-271-615; fax: +44-1865-271-853
Objective: Recent evidence shows that calcium released from the sarcoplasmic reticulum (SR) plays an important role in the regulation of heart rate. The aim of this study was to investigate the subcellular distribution of ryanodine receptors in the guinea-pig sino-atrial (SA) node and to determine their functional role in the regulation of pacemaker frequency in response to β-adrenoceptor stimulation. Methods: Monoclonal antibodies raised against the cardiac ryanodine receptor were used with confocal microscopy to investigate ryanodine receptor distribution in single guinea-pig SA node cells. The functional role of ryanodine receptors was investigated in both multicellular SA node/atrial preparations and in single SA node cells. Results: Ryanodine receptor labelling was observed in all SA node cells studied and showed both subsarcolemmal and intracellular staining. In the latter, labelling appeared as transverse bands with a regular periodicity of 
2 µm. This interval resembled that of the expected sarcomere spacing but did not, however, depend on the presence of transverse tubules. The bands of ryanodine receptors appeared to be located in the region of the Z lines, based on co-distribution studies with antibodies to 
-actinin, myomesin and binding sites for phalloidin. Functional studies on single SA node cells showed that application of ryanodine (2 µmol/l) reduced the rate of firing of spontaneous action potentials (measured using the perforated patch clamp technique) and this was associated with changes in action potential characteristics. Ryanodine also significantly decreased the positive chronotropic actions of isoprenaline in both multicellular and single cell preparations. In single cells exposed to 100 nmol/l isoprenaline, ryanodine caused a decrease in the rate of firing and this was associated with a decrease in the amplitude of the measured calcium transients. Conclusions: These findings are the first to show immunocytochemical evidence for the presence and organisation of ryanodine receptor calcium release channels in mammalian SA node cells. This study also provides evidence of a role for ryanodine sensitive sites in the β-adrenergic modulation of heart rate in this species.
KEYWORDS SR (function); Calcium (cellular); Heart rate (variability); Receptors; Sinus node
1 Dr. Yi Cui has now moved to The Rayne Institute, University College London, London, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Wu, Z. Gao, B. Chen, O. M. Koval, M. V. Singh, X. Guan, T. J. Hund, W. Kutschke, S. Sarma, I. M. Grumbach, et al. From the Cover: Calmodulin kinase II is required for fight or flight sinoatrial node physiology PNAS, April 7, 2009; 106(14): 5972 - 5977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Vinogradova, S. Sirenko, A. E. Lyashkov, A. Younes, Y. Li, W. Zhu, D. Yang, A. M. Ruknudin, H. Spurgeon, and E. G. Lakatta Constitutive Phosphodiesterase Activity Restricts Spontaneous Beating Rate of Cardiac Pacemaker Cells by Suppressing Local Ca2+ Releases Circ. Res., April 11, 2008; 102(7): 761 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Maltsev and E. G. Lakatta Dynamic interactions of an intracellular Ca2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function Cardiovasc Res, January 18, 2008; (2008) cvm058v3. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Choate, S. M. Murphy, R. Feldman, and C. R. Anderson Sympathetic control of heart rate in nNOS knockout mice Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H354 - H361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mattick, J. Parrington, E. Odia, A. Simpson, T. Collins, and D. Terrar Ca2+-stimulated adenylyl cyclase isoform AC1 is preferentially expressed in guinea-pig sino-atrial node cells and modulates the If pacemaker current J. Physiol., August 1, 2007; 582(3): 1195 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Heaton, M. Lei, D. Li, S. Golding, T. A. Dawson, R. M. Mohan, and D. J. Paterson Remodeling of the Cardiac Pacemaker L-Type Calcium Current and Its {beta}-Adrenergic Responsiveness in Hypertension After Neuronal NO Synthase Gene Transfer Hypertension, September 1, 2006; 48(3): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sanders, S. Rakovic, M. Lowe, P. A. D. Mattick, and D. A. Terrar Fundamental importance of Na+-Ca2+ exchange for the pacemaking mechanism in guinea-pig sino-atrial node J. Physiol., March 15, 2006; 571(3): 639 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A V Postma, I Denjoy, J Kamblock, M Alders, J-M Lupoglazoff, G Vaksmann, L Dubosq-Bidot, P Sebillon, M M A M Mannens, P Guicheney, et al. Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients J. Med. Genet., November 1, 2005; 42(11): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Vinogradova, Y.-Y. Zhou, V. Maltsev, A. Lyashkov, M. Stern, and E. G. Lakatta Rhythmic Ryanodine Receptor Ca2+ Releases During Diastolic Depolarization of Sinoatrial Pacemaker Cells Do Not Require Membrane Depolarization Circ. Res., April 2, 2004; 94(6): 802 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Silva and Y. Rudy Mechanism of Pacemaking in IK1-Downregulated Myocytes Circ. Res., February 21, 2003; 92(3): 261 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Lakatta, V. A. Maltsev, K. Y. Bogdanov, M. D. Stern, and T. M. Vinogradova Cyclic Variation of Intracellular Calcium: A Critical Factor for Cardiac Pacemaker Cell Dominance Circ. Res., February 21, 2003; 92 (3): e45 - e50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Postma, I. Denjoy, T. M. Hoorntje, J.-M. Lupoglazoff, A. Da Costa, P. Sebillon, M. M.A.M. Mannens, A. A.M. Wilde, and P. Guicheney Absence of Calsequestrin 2 Causes Severe Forms of Catecholaminergic Polymorphic Ventricular Tachycardia Circ. Res., October 18, 2002; 91 (8): e21 - e26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O Verkerk, R. Wilders, J. G Zegers, M. M G J van Borren, J. H Ravesloot, and E E. Verheijck Ca2+-activated Cl- current in rabbit sinoatrial node cells J. Physiol., April 1, 2002; 540(1): 105 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Musa, M. Lei, H. Honjo, S. A. Jones, H. Dobrzynski, M. K. Lancaster, Y. Takagishi, Z. Henderson, I. Kodama, and M. R. Boyett Heterogeneous Expression of Ca2+ Handling Proteins in Rabbit Sinoatrial Node J. Histochem. Cytochem., March 1, 2002; 50(3): 311 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Herring, L. Rigg, D. A Terrar, and D. J Paterson NO-cGMP pathway increases the hyperpolarisation-activated current, If, and heart rate during adrenergic stimulation Cardiovasc Res, December 1, 2001; 52(3): 446 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Protas, D. DiFrancesco, and R. B. Robinson L-type but not T-type calcium current changes during postnatal development in rabbit sinoatrial node Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1252 - H1259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M Bryant, C. E Sears, L. Rigg, D. A Terrar, and B. Casadei Nitric oxide does not modulate the hyperpolarization-activated current, If, in ventricular myocytes from spontaneously hypertensive rats Cardiovasc Res, July 1, 2001; 51(1): 51 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Lakatta Heart Aging : A Fly in the Ointment? Circ. Res., May 25, 2001; 88(10): 984 - 986. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Vinogradova, K. Yu. Bogdanov, and E. G. Lakatta {beta}-Adrenergic Stimulation Modulates Ryanodine Receptor Ca2+ Release During Diastolic Depolarization to Accelerate Pacemaker Activity in Rabbit Sinoatrial Nodal Cells Circ. Res., January 11, 2002; 90(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|