Alterations in cardiac excitation contraction coupling in ventricular myocytes from aging hearts and myocytes from hearts that overexpress beta adrenergic receptors.
Date
2005
Authors
Grandy, Scott A.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Cardiac excitation contraction (EC) coupling is the process whereby the depolarization of the sarcolemma results in a transient increase in intracellular Ca2+ and ultimately cardiac contraction. Several studies have suggested that cardiac contractile function is altered with advancing age. In aged ventricular myocytes, contraction and Ca2+ transient amplitudes are reasonably well preserved at rest, but the effects of aging on L-type Ca2+ current (ICa-L) are unclear. Furthermore, the relationship between contraction and ICa-L in aging heart has not been examined. Therefore, the first objective of this study was to simultaneously measure amplitudes of contraction and ICa-L in voltage clamped young adult and aged murine ventricular myocytes at physiological temperatures to determine the effects of aging on EC coupling. Results showed that contraction amplitudes, ICa-L amplitudes and Ca2+ transient amplitudes were significantly reduced in aged myocytes paced at 2 Hz. However, the gain of CICR, which is the amount of calcium released from the sarcoplasmic reticulum (SR) per nA of ICa-L, was similar in young adult and aged myocytes. This suggests that the relationship between ICa-L and contraction was not altered in aged myocytes. The present study also found that SR Ca2+ stores were similar in young adult and aged myocytes. The second objective of this study was to characterize the relationship between ICa-L, SR Ca2+ release and contraction in TG4 myocytes at physiological temperatures. Results showed that contraction amplitudes were significantly greater in field-stimulated TG4 myocytes than in WT myocytes. However, contraction amplitudes were similar in voltage clamped WT and TG4 myocytes, despite a significant reduction in the magnitude of ICa-L in TG4 myocytes. Peak Ca2+ transient amplitudes also were similar in voltage clamped WT and TG4 myocytes. Since peak contraction and Ca 2+ transient amplitudes were maintained despite a reduction in I Ca-L, this suggests that the gain of CICR was increased in TG4 myocytes. Furthermore, SR Ca2+ stores were significantly increased in TG4 myocytes. Thus, it is possible that the increased gain of CICR in TG4 myocytes is attributable, in part, to increased SR Ca2+ load. Together, these results suggest that contraction amplitude is maintained in TG4 myocytes by an increase in the gain of CICR. (Abstract shortened by UMI.)
Thesis (Ph.D.)--Dalhousie University (Canada), 2005.
Thesis (Ph.D.)--Dalhousie University (Canada), 2005.
Keywords
Health Sciences, Pharmacology.