J Physiol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 580, Number 2, 543-560, April 15, 2007 DOI: 10.1113/jphysiol.2006.123729
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental data
Right arrow All Versions of this Article:
580/2/543    most recent
jphysiol.2006.123729v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nygren, A.
Right arrow Articles by Shimoni, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nygren, A.
Right arrow Articles by Shimoni, Y.
Related Collections
Right arrow Cardiovascular

CARDIOVASCULAR

Propagation of the cardiac impulse in the diabetic rat heart: reduced conduction reserve

 A. Nygren2, M. L. Olson1, K. Y. Chen1, T. Emmett1, G. Kargacin1 and Y. Shimoni1

1 Department of Physiology and Biophysics
2 Department of Electrical and Computer Engineering, University of Calgary, Alberta, Canada

Diabetes mellitus is a growing epidemic with severe cardiovascular complications. Although much is known about mechanical and electrical cardiac dysfunction in diabetes, few studies have investigated propagation of the electrical signal in the diabetic heart and the associated changes in intercellular gap junctions. This study was designed to investigate these issues, using hearts from control and diabetic rats. Diabetic conditions were induced by streptozotocin (STZ), given I.V. 7–14 days before experiments. Optical mapping with the voltage-sensitive dye di-4-ANEPPS, using hearts perfused on a Langendorff apparatus, showed little change in baseline conduction velocity in diabetic hearts, reflecting the large reserve of function. However, both the gap junction uncoupler heptanol (0.5–1 mM) and elevated potassium (9 mM, to reduce cell excitability) produced a significantly greater slowing of impulse propagation in diabetic hearts than in controls. The maximal action potential upstroke velocity (an index of the sodium current) and resting potential was similar in single ventricular myocytes from control and diabetic rats, suggesting similar electrical excitability. Immunoblotting of connexin 43 (Cx43), a major gap junction component, showed no change in total expression. However, immunofluorescence labelling of Cx43 showed a significant redistribution, apparent as enhanced Cx43 lateralization. This was quantified and found to be significantly larger than in control myocytes. Labelling of two other gap junction proteins, N-cadherin and beta-catenin, showed a (partial) loss of co-localization with Cx43, indicating that enhancement of lateralized Cx43 is associated with non-functional gap junctions. In conclusion, conduction reserve is smaller in the diabetic heart, priming it for impaired conduction upon further challenges. This can desynchronize contraction and contribute to arrhythmogenesis.

(Received 24 October 2006; accepted after revision 18 December 2006; first published online 21 December 2006)
Corresponding author Y. Shimoni, Health Sciences Centre, 3330 Hospital Dr. N.W., Calgary, AB, Canada T2N 4N1.  Email: shimoni{at}ucalgary.ca

A. Nygren, G. Kargacin and Y. Shimoni contributed equally to this work.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 The Physiological Society.