| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 School of Biomedical Sciences
2
School of Sport and Exercise Sciences, University of Leeds, Leeds LS2 9JT, UK
Clinical studies have shown that sinoatrial node dysfunction occurs at the highest incidence in the elderly population. Guinea-pigs were studied throughout their lifespan (i.e. birth to 38 months) to investigate the possible mechanism leading to nodal dysfunction. Using immunofluorescence with confocal microscopy, Cx43 protein expression was shown at birth to be present throughout the sinoatrial node and atrial muscle, however, at one month Cx43 protein was not expressed in the centre of the sinoatrial node. Throughout the remainder of the animal's lifespan the area of tissue lacking Cx43 protein progressively increased. Western blot provided verification by quantitative analysis that Cx43 protein expression within the sinoatrial node decreased with age; however, the expression of other cardiac connexins, Cx40 and Cx45, did not differ with age. Analysis of conduction maps showing propagation of the action potential across the sinoatrial node, from the initiation point to the crista terminalis, found that the action potential conduction time taken and conduction distance increased proportionally with age; conversely the conduction velocity decreased with age. We have shown ageing induces degenerative changes in action potential conduction, contributed to by the observed loss of Cx43 protein. Our data identify Cx43 as a potential therapeutic target for quashing the age-related deterioration of the cardiac pacemaker.
(Received 16 July 2004;
accepted after revision 9 August 2004;
first published online 12 August 2004)
Corresponding author S. A. Jones: School of Biomedical Sciences, Worsley Medical Building, University of Leeds, Leeds LS2 9JT, UK. Email: s.a.jones{at}leeds.ac.uk
This article has been cited by other articles:
|
|
 |
|
  D. D. Christou and D. R. Seals Decreased maximal heart rate with aging is related to reduced {beta}-adrenergic responsiveness but is largely explained by a reduction in intrinsic heart rate J Appl Physiol, July 1, 2008; 105(1): 24 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Jones, M. Yamamoto, J. O. Tellez, R. Billeter, M. R. Boyett, H. Honjo, and M. K. Lancaster Distinguishing Properties of Cells From the Myocardial Sleeves of the Pulmonary Veins: A Comparison of Normal and Abnormal Pacemakers Circ Arrhythmia Electrophysiol, April 1, 2008; 1(1): 39 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Baruscotti and R. B. Robinson Electrophysiology and pacemaker function of the developing sinoatrial node Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2613 - H2623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dobrzynski, M. R. Boyett, and R. H. Anderson New Insights Into Pacemaker Activity: Promoting Understanding of Sick Sinus Syndrome Circulation, April 10, 2007; 115(14): 1921 - 1932. [Full Text] [PDF]
|
|
|
|
|
|
K. Boengler, I. Konietzka, A. Buechert, Y. Heinen, D. Garcia-Dorado, G. Heusch, and R. Schulz Loss of ischemic preconditioning's cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43 Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1764 - H1769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Haqqani and J. M. Kalman Aging and Sinoatrial Node Dysfunction: Musings on the Not-So-Funny Side Circulation, March 13, 2007; 115(10): 1178 - 1179. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Jones, M. R. Boyett, and M. K. Lancaster Declining Into Failure: The Age-Dependent Loss of the L-Type Calcium Channel Within the Sinoatrial Node Circulation, March 13, 2007; 115(10): 1183 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Baba, W. Dun, M. Hirose, and P. A. Boyden Sodium current function in adult and aged canine atrial cells Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H756 - H761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, X. Chen, D. Wu, W. Liu, J. Wang, Z. Feng, G. Cai, B. Fu, Q. Hong, and J. Du Downregulation of Connexin 43 Expression by High Glucose Induces Senescence in Glomerular Mesangial Cells J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1532 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Gutstein, S. B. Danik, S. Lewitton, D. France, F. Liu, F. L. Chen, J. Zhang, N. Ghodsi, G. E. Morley, and G. I. Fishman Focal gap junction uncoupling and spontaneous ventricular ectopy Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1091 - H1098. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
